Introduction to Medical Physiology PDF January 2025

Cynthia C. Bennett, MD January 2025 Introduction to Medical Physiology  Today’s Instructional Objectives: Day 1: Introduction/Homeostasis 1. Explain the concept of homeostasis completely. 2. Explain the difference between constancy, e...

Cynthia C. Bennett, MD January 2025 Introduction to Medical Physiology  Today’s Instructional Objectives: Day 1: Introduction/Homeostasis 1. Explain the concept of homeostasis completely. 2. Explain the difference between constancy, equilibrium and homeostasis. 3. State the distribution of water in the human body and understand its importance. 4. Explain how osmosis, diffusion, active transport and other transport methods are used to maintain homeostasis. 5. Explain the roles and relative frequency of positive and negative feedback in maintenance of homeostasis. 6. List the properties of the cell membrane and the roles of the other major organelles. 7. List the four major methods of cellular communication. 8. Describe the mechanics of aerobic respiration and its necessity in human physiology- specifically: a. that the process involves the steps of glycolysis, the citric acid (Krebs) cycle and oxidative phosphorylation (the electron transport chain) and know in brief what happens in each of these steps b. where, and how, oxygen is utilized in this process. c. where, and how, carbon dioxide is produced in this process. d. why this process cannot occur without oxygen. 9. Diagram the organization patterns of the human body from cell to organism. 10. Explain why surface area, and a high surface-to-volume ratio, is imperative in multicellular organisms. 11. List the major organ systems of the human body and their roles within the body. 12. List the 4 basic tissue types of the human body and the roles they play. 13. List the types of intracellular junctions and their characteristics and uses. 14. Recognize the differences in positive and negative feedback loops and be able to explain their terminology.  HOMEOSTASIS …QUICK! What words are VITAL to its definition? [2 minutes]  Homeostasis: A framework for human physiology 4 “Homeostasis refers to the dynamic mechanisms that detect and respond to deviations in physiologic variables from their “set point” values by initiating effector responses that restore the variables to the optimal physiological range.”  GREEK: ὅμοιος, hómoios, "similar”, and στάσις, stásis, "standing still" The Maintenance of Steady States in the Body by Coordinated Physiologic Mechanisms. An energy-consuming process. “The art of moving to stay the same.” “Running to stand still.” QUICK! (2 minutes) Explain the statement below.  Body Fluid Terminology— These numbers apply to AVERAGE ADULT PATIENTS and are APPROXIMATIONS. Have you heard that your body is about 2/3 water? ******* Homeostasis uses water …and its dissolved substances to create a steady state. Do you remember learning the historical importance of water to the growth of a big city? Water is equally important as the transporter and communicator within the human body.  Body Fluid Terminology— These numbers apply to AVERAGE ADULT PATIENTS. 9  “body fluids” = the watery solution of dissolved substances (oxygen, nutrients, etc.) present in the body. Fluids can be divided into Intracellular Fluid (ICF) and Extracellular Fluid (ECF).  Extracellular Fluid (ECF) =The fluid in the blood and surrounding the cells (i.e., outside the cell).  About 25% of ECF is in the fluid portion of blood (plasma) and the remaining 75% of the ECF lies around and between cells and is known as the interstitial fluid.  The space containing interstitial fluid is called the interstitium or interstitial space. Therefore, the total volume of ECF is the sum of the plasma and interstitial volumes.  ECF = plasma + interstitial If an adult patient weighs 150 pounds, then… assuming that 60% of one’s weight is water:  What does their total body water weigh? 90 lb  What poundage of this is in the intracellular space? 60 lb  What poundage of this is extracellular? 30 lb  How much does this patient’s plasma fluid weigh? 7.5 lb  Figure 1-3 ICF ISF plasma organs external environment internal environment Exchange across a plasma membrane is key to understanding physiological homeostasis. 11  Body Fluids and Compartments 12 The composition of Extracellular Fluid (ECF) is very different from that of the Intracellular Fluid (ICF).  Maintaining differences in fluid composition across the cell membrane is a major way that cells regulate their own activity.  QUICK! Think of one example of cell function that requires the cell to be “different inside” than its outer surroundings. (1 min) Let’s Talk About Membranes …starting with the cell membrane.  The Fluid-Mosaic Model of a Cell Membrane: A cell membrane is a fluid structure. We’re not fluid, but each of our cells are. Cell membranes have areas of decreased movement, where they’re “anchored” to the cytoplasm. Phospholipids move around these areas like the plastic duckies at the carnival. How can you be a solid person made up of liquids encased in liquid membranes? Well… The Cell Membrane: selectively permeable Notice… this one is a glycoprotein! Consider: (1 min) What molecules can pass right through? What molecules can pass through passively if “assisted”? What molecules need to be actively shuttled across? What molecules need a membrane “packaging” to get in or out?  Surrounding the cells: Fluid and ECM 17  The immediate environment that surrounds each individual cell in the body is the extracellular fluid and extracellular matrix (ECM).  ECM is a mixture of proteins, polysaccharides, and in some cases (e.g. bone), minerals.  The matrix serves two general functions: (1) It provides a scaffold for cellular attachments, and (2) it transmits information, in the form of chemical messengers, to– and between-- the cells.  The proteins of the extracellular matrix consist of ropelike collagen fibers and rubber-band-like elastin fibers—and a mixture of nonfibrous proteins that contain carbohydrate. The “Medievil Castle” theory of the cell: QUICK: (take 1 minute to think about these) What does it What does need to What does it it need to KEEP IN or need to send bring in? KEEP OUT? out?  The Tools of the Cell: Cell Membrane and its proteins Construction sites (ER, Cytoplasm) Cytoskeleton and motor proteins Command Center (nucleus) Storage sites (vacuoles, SR) Reproductive parts (centromere) Mitochondria The Inner Life of The Cell Osmosis: diffusion of water across a cell membrane. Quick! (1 min) If you put a red blood cell in each of these solutions, which way will water travel across the cell membrane—and why? Isotonic Hypertonic Hypotonic Remember: In osmosis and diffusion, movement is always happening– even when equilibrium has been reached. While the goal is equilibrium, because of this movement the concentration is “wiggling” on each side of the membrane but “averaging” at the equilibrium point.  Remember: In active transport, movement is happening against the concentration gradient. THIS PROCESS REQUIRES: ENERGY (ATP!!) A TRANSPORT/ CARRIER PROTEIN Memes: makeameme.org  PRACTICE QUESTION! In questions like this, assume that the cell’s content is finite and the solution’s volume is infinite.  PRACTICE QUESTION: 1 mmol out here The only way a substance can travel against its concentration gradient is by 5 mmol in active transport. here In questions like this, assume that the cell’s content is finite and the solution’s volume is infinite. Wash your hands. Drown a Germ. --”Drown”? Explain what happens by considering that “germs” are now being placed into a hypo-osmolar environment. Check in: How are you feeling? Other Organelles  I’ll assume you know a one-sentence explanation of the role of every organelle.  We will focus on just a couple besides the plasma membrane. Mitochondria– the powerhouses. Explain: Why must ALL your mitochondria come from your mom? Note: --Outer membrane --Inner membrane, folded, with lots of transmembrane proteins --TONS of ribosomes! (why?) Where does our energy come from? AEROBIC RESPIRATION- The Brief Version: 34 ATP molecules for every 1 molecule of glucose, vs. the 4:1 return in anaerobic respiration Which human body cells do the most aerobic respiration? (liver and muscle) This process is dependent on: oxygen, glucose or another burnable material, membrane integrity, correct pH, functioning enzymes. Mitochondria need Substrate. The most common substrate is glucose. 1. What happens to the glucose during glycolysis? 2. What else must happen for the glucose to be used in the Citric Acid Cycle?  The Kreb’s Cycle: Where’s the ATP? Please know the basics of this cycle. You only have to know the names that are circled. 6 carbons 6 carbon thing 4 carbons Pick up AcCoA, become a 6 carbon thing again 5 carbons 4 carbons The Krebs 5 carbon thing Cycle Several different 4 carbons 4 carbon things… 4 carbon thing The Kreb’s Cycle: Where’s the ATP? 6 carbons Only a little bit of 4 carbons ATP is being produced here– 4 carbons 5 carbons but a LOT of NADH and FADH2… 4 carbons 4 carbons  Mitochondria need Oxygen. …And the NADH and FADH2 then travel via diffusion to the electron transport chain. There, they participate in a series of reactions that create ATP– A LOT OF ATP. Explain: -- When is oxygen used here? --Why is it needed?  Mitochondria need Oxygen. This protein is a channel NADH built especially for H+ and Protons (H+) get sent up here ions. FADH2 As they travel through it arrive to back into the the mitochondrion.. mitochon drion.. Its “wheel” turns, producing energy. The This protein energy attaches P to splits the H ‘s Electrons get shuttled along here ADP, making ATP– LOTS. single proton (H+) and electron (-) off The H+ and the shuttled of NADH and electrons attach to O2, FADH1. to become H2O. Watch this gif if you’re not sure. ☺ Fun fact: Mitochondria can be poisoned. Rotenone Cyanide, Oligomycin carbon monoxide H+ H+ H+ H+ ATP H+ H+ H+ synthase DNP FADH2 FAD 1 − O2 + 2 H+ NADH NAD+ 2 H+ H+ ADP + P ATP H2O H+ Electron Transport Chain Chemiosmosis Break!  THIS HOUR: Cell Signaling Why Multicellular? Tissue vs. Organ vs. Organ System Feedback Loops New topic: CELL SIGNALING Cells need a way to talk to each other. New topic: CELL SIGNALING autocrine, paracrine, endocrine, and nervous/ neurocrine. AUTOCRINE: Cells talking to themselves. -Many cells use this as a method of negative feedback— If there’s enough signaling molecule around to bind to the autocrine receptor, then the cell should save its energy and quit making it.  PARACRINE Short distance signals Messenger chemicals have a short lifespan Messengers have high specificity to their receptors (no mistakes) A VERY COMMON PARACRINE SIGNALLER: Nitric Oxide  When you hear “nitrogen” think of amino acids and proteins. The result? The vascular lining cell just “told” the cells of the vessel’s muscular lining to relax. NO is made by almost all cells– including the endothelial cells lining blood vessels. Formed when the endothelial cells break an N off of an amino acid, and attach it to an O. NO is fairly nonpolar, so it diffuses passively through the endothelial cell’s membrane … And into the smooth muscle cell beneath it. There, it activates a signal amplification system that uses something like ATP for energy… And that system causes the muscle cell to store its calcium away. When Ca++ levels go down in the muscle cell, the cell can’t contract– so the muscular wall of the vessel relaxes.  Absorbed into bloodstream, where it… Breaks down to NO, which… Diffuses into smooth muscle cells of coronary arteries, thus… Dilating coronary arteries. AND it also…  Why does this work? Relaxing smooth muscle of peripheral vascular beds. (1 minute) ENDOCRINE: cells talking to other cells from near to far. Messenger chemical lifespans vary from a few minutes (protein hormones) to several days (steroid hormones). Messengers have lower specificity for their receptors than the paracrine ones (make sure the message gets through). Goal is for one organ in the body to give guidance across many cell/organ types, and to elicit many different responses. NEUROENDOCRINE: when the nervous system talks directly with the endocrine system In general, the nervous system is the “fast” human body regulator and the endocrine system is the “slow” human body regulator. They usually work parallel to each other. In a few select places, the two systems talk directly– usually with the nervous system “transferring” its information into an endocrine message. The result? A longer lasting, but still rapid and strong, message. We are multicellular... Not giant amoebas. Because it takes time to get substances transported to all areas of a single cell. THIS Could never exist, because the middle of the giant cell would die if substances can’t get to it in a timely manner. A High Surface-to-Volume Ratio is Key to a Cell’s Survival. That’s why large organisms are multicellular. …and why big ice cubes have become a thing. If you don’t want that, use giant ice cubes More surface area = more melt into your drink. instead. And that’s why every cell in the human body is within a few cell layers of a capillary, and every cell is in contact with interstitial fluid.  Cellular Connection Types: Cells have the connections that work best for their purpose. Tight Junctions: What cells might use “water-tight sealant.” these? Desmosomes: “spot- welding” with lots of What cells might use strength. these? Gap Junctions: a “cellular strainer”. What cells might use these?  Cells in multicellular organisms are not independent. Each cell type has its job to do. Cells of the same cell type work Different cell types work together together to do their part of a job. to get the larger job done.  Cells can be “Clumped” into four functional groups, called TISSUE TYPES: For this class, know the 4 types and a few examples of each. These are the “lego blocks” of the organ-building world. Each does a particular type of job. Muscle tissue Nerve tissue  Connective tissue– Cells within a noncellular matrix.  Epithelial Tissue- Like a nice suit, every part of the human body has a lining. Organs and Organ Systems: …cells of different tissue types working together.  Now, with all this knowledge… let’s look at Homeostasis and Physiology “Normal” in physiology typically is a range around a median point range. Physiologic mechanisms allow variables to always be dynamic by requiring that they stay within a set “normal” range- not at one “normal” point. Cells, organs, and systems can all have a physiologic range that is their homeostasis “set point.” “Normal” = “Set Point” Strays from normal when it needs to… comes back to its set point.  Homeostasis exists to help put an organism’s variables back into its range of “normal.” This is called “Dynamic Constancy”: levels vary over the short term, but are relatively stable over the long haul. Variables need to be dynamic, because organisms need to be able to stray from “normal” when change is necessary.  System “inputs and outputs” are managed by Feedback Loops. 65  Feedback loops are a common mechanism to control physiological processes.  A positive feedback loop enhances the Positive Feedback= yes, production of the product. then YES  A negative feedback system shuts the Negative Feedback = system off once the set point has been Yes, then NO reached. WHICH IS MORE COMMON IN HOMEOSTASIS???  A strategy for exploring homeostasis 66 This is the 1. Identify the internal environmental variable- and there are thousands! BE SPECIFIC. stimulus example: concentration of glucose in the blood 2. Establish the “set point” range of normal for that variable. example: 70 to 110 mg glucose/dL of blood This is the 3. Determine how the body monitors/senses the variable. sensor example: cells in the pancreas detect changes in blood glucose levels 4. Identify effectors that restore the variable to its set point. This is the example: glucagon is released, increasing glucose synthesis by the liver response Lastly: Identify the inputs and outputs affecting the variable, and the balance of those inputs and outputs. example: diet and energy metabolism example: resting versus exercising, eating vs fasting How are these inputs and outputs affecting the variable? Sending it too high? Too Low? Explained the simple way: Start here [BOGObiology]. (2016, December 3. 5 Minute Bio – Homeostasis. [Video File]. Retrieved from https://youtu.be/kAy-03hIfck Explained the physiologic way: Affect (stimulus) Here, the sensor is cutaneous peripheral sensory nerves Responses Effect Normalization of this variable will turn off the stimulus.  Figure 1-6 Affect Negative Feedback: Explain Your body this has LOTS of ways of diagram to modifying your these loops. neighbor. A common [2 min] one: MULTI- STEP Effect PROCESSES. “Active product” controls the sequence of chemical reactions by inhibiting the sequence’s rate-limiting enzyme, “Enzyme A.” Intermediates are an opportunity for outside forces to either increase or decrease the amount of active product. Endocrine and Nervous systems are great big feedback loops. More on these later! The classic reflex arc is a negative feedback mechanism. When the stimulus stops, the response stops too. Endocrine feedback loops also follow this pattern. These systems mostly involve MUSCLES AND NERVES. These systems mostly involve GLANDS, HORMONES AND TARGET ORGANS.  Physiology vs. Pathophysiology 71 ▪ Physiological variables can change dramatically over a 24-hr. period, but in physiology the system remains in overall balance. ▪ When homeostasis is maintained over time, we call it physiology; when it is not, we call it pathophysiology. Check in: Now how are you feeling? That’s it for today!  Tomorrow: