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Unformatted text preview: Table of Contents Chapters/Topics Introduction Chapter 1 Reading & Study Questions Chapter 2 Chemistry Review Chapter 3 Cells & Tissues Review Chapter 4 Energy & Cell Metabolism Review Chapter 5 Membrane & Transport Reading & Study Questions Membrane & Epithelial Transport Problems Solutions, Osmolarity & Tonicity Guide Single Cell Tonicity Problems Solutions, Osmolarity & Tonicity Practice problems Solutions, Osmolarity & Tonicity Discussion Exercise Chapter 6 Communication & Control Reading & Study Questions Chapter 7 Endocrine Reading & Study Questions Signaling & endocrine Problems Endocrine Discussion Exercise Neurophysiology Review (Chapters 8- 11) Neurophysiology Problems Chapter 12 Muscle Review Chapter 14 CV I Reading & Study Questions Chapter 15 CV II Reading & Study Questions CV Problems CV Class exercise CV Discussion exercise Chapter 17- 18 Respiration Reading & Study Questions Respiration Problems Integrated CV & Resp Problems Chapter 19 Renal & Ch 20 Fluid/electrolyte balance Reading & Study Questions Renal Problems Renal Discussion Exercises Chapter 20 Acid- Base Reading & Study Questions Acid- Base Problems Acid- Base Discussion Exercise Chapter 21- 23 Reading & Study Questions Metabolism & Digestion Problems Answer Key for Numbered Problems 1 Pages 2 – 3 4 5 5 – 6 7 8 9 – 12 13 – 23 24- 26 27- 29 30- 31 32 32- 34 35- 37 38 39- 40 41- 42 43 44- 48 49- 52 53- 55 56 57- 58 59- 62 63- 64 65- 66 67- 71 72- 73 74- 75 76- 78 79 80- 81 82- 84 85- 86 88- 96 365S Study Guide Spring 2012 Dr. McAnelly Before attempting the problems in the Study Guide, please read the assigned material in your text. As you read the text, pay attention to vocabulary and definitions, tables and graphs and try to answer the figure and concept check questions in each chapter. This study guide is meant to supplement, not replace, review material in your textbook.. There will be quizzes assigned in MasteringA&P that are also intended to help you assess how well you understand the material. This Study Guide is an additional tool to help you learn how to solve problems related to the material that we will cover the text, in class and in discussion. Answers are provided for the numbered questions in the back of this booklet. Not all of the questions in this booklet will be in the answer key. Work through the problems first before checking the answers. Peeking at the answers is like sitting on the couch trying to lose weight by watching “The Biggest Loser”. It won’t help you achieve your goal and in fact may prevent you from doing so. HOW TO USE THIS WORKBOOK Pre- class Reading Questions These are designated with the following format: 1.1, 1.2, etc, where the first number is the chapter number and the number after the period is the question number. These questions cover the information you should be familiar with BEFORE you come to class. They are designed to guide your reading in the text. Answer the questions as you read. You do not need to write the answers but you may find it helpful in learning the information. Make notes of questions you have and points that are unclear so that we can discuss them in class. Be sure to bring the pages for what we’re covering to class each time. The answers to the reading questions are found or can be deduced from the material within the textbook. Numbered Problems: This workbook has a number of problems and questions from old tests. These are grouped into topics and numbered. Answers for these questions are found in the answer key at the end of this booklet. Discussion Exercises. You will work on these during your discussion sessions. Please bring the appropriate pages from this study guide with you to discussion session. Some discussion exercises are not included in this study guide and will be posted separately on Bb Homework. There are three homework assignments that you will turn in for a grade. They will be posted separately on Bb. 2 HOW TO USE THE TEXT: (text p. xxiii) • What feature of the book allows you to compare your background knowledge to that needed to master each chapter? ____________________________________________________________________ • What is the function of the blue page numbers? ____________________________________________________________________________________ • A figure that has a graph has a question about the graph associated with it. Where would you find the answer to that question so that you can check to see if you answered it correctly? ____________________________________________________________________________________ • The Concept Check questions act as ‘speed bumps’ to make you think about what you just read. Where do you find the answers to these?_____________________________________________ • Where do you find answers to the questions at the end of each chapter? ___________________________ 3 CHAPTER 1 READING QUESTIONS 1.1 List the ten levels of organization, starting with atoms and ending with the biosphere. (Fig. 1- 1) 1.2 List the ten human organ systems. (Table 1- 1 and accompanying figure) 1.3 Distinguish between extracellular fluid and intracellular fluid. (Fig. 1- 4, 1.6) 1.4 Define homeostasis. Who coined the term homeostasis? 1.5 What happens when the body is unable to maintain homeostasis? What are some factors that might contribute to a failure of homeostasis? (Fig. 1- 3) 1.6 How does mass balance relate to homeostasis? 1.7 What is clearance? What organs are involved in clearance? 1.8 What is mass flow? Write an equation for mass flow. 1.9 List and briefly describe the major physiological themes discussed in this book. (Table 1- 2) 1.10 For the theme of Biological Energy (see Chapter 4, pp. 99- 101) – Where does energy come from? – How is energy stored? – Energy is the capacity to do work. Biological work takes 3 basic forms: Chemical work Transport work Potential energy is stored in concentration gradients. Mechanical work 1.11 Information flow in the body takes what forms? 1.12 Differentiate between local communication and long- distance communication in the body. 1.13 How/where is genetic information stored? 1.14 Communication between intracellular compartments and the extracellular fluid requires ...? 1.15 Describe and draw a simple control system. What are regulated variables (Fig. 1- 5) 1.16 What do we mean when we say that a membrane is selectively permeable? ✔ Match each term with the two best answers: teleological approach _________ a) process b) function mechanistic approach _________ c) how d) why ✔ A student says, “When I exercise and breathe faster, it’s because my cells need more oxygen.” Is this a mechanistic or teleological explanation of why one breathes faster with exercise? Defend your answer. 4 Review: Chapter 2 Reading Questions This chapter should be a review of your chemistry classes. If you can’t answer the questions below, review Chapter 2 in the book. 2.1 Match the following _____ atomic mass A. molecule that contains more than one element _____atomic number B. protons plus neutrons _____isotopes C. capture and transfer energy _____electrons D. number of protons _____radioisotopes E. atoms with different numbers of protons _____atomic mass unit F. negatively charged ion _____compound G. energy emitted by radioisotope _____anion H. atom gains or loses electrons _____cation I. two or more atoms that share electrons _____covalent bond J. a pair of electrons shared by two electrons _____ion K. atoms with different numbers of neutrons _____molecule L. Dalton _____elements M. positively charged ion _____radiation N. unstable isotopes 2.2 How do you make up 200 mL of 5% dextrose (=glucose C6H12O6) solution? 2.3 Define ligand, substrate, and specificity. 2.4 What is meant when we say that a protein has an affinity for a particular ligand? 2.5 Using both words and a quantitative representation, describe equilibrium. 2.6 Now describe how a dissociation constant relates to protein- ligand interactions. 2.7 What are competitors? agonists? antagonists? inhibitors? isoforms? 2.8 What is allosteric modulation? 2.9 How does the body use up- regulation and down- regulation to maintain appropriate protein levels? 2.10 What is saturation as it applies to protein- ligand interactions? How is it related to the reaction rate? 2.11 Understand factors that influence protein activity (Fig 2.13). 2.12 Review p. 44- 45 on how to make solutions. You will have problems later that involve knowing how to make up per cent solutions, solutions of given molarity, etc. 2.13 Review molecular bonds (Fig 2.6, p42) REVIEW: CHAPTER 3 READING QUESTIONS This chapter reviews background information that you should have learned in Introductory Biology. 3.1 What are the anatomical and functional body compartments? - What are the three major body cavities? - What major organs do you find in each? (Fig. 3- 1A) 3.2 Define and describe the term lumen. 5 3.3 What do we mean when we say that, for some organs, the lumen is essentially an extension of the external environment? (Fig. 3- 9) 3.4 Extracellular fluid can be subdivided into_______ and _________. (Fig. 3- 2) 3.5 What are two meanings of the term “membrane” in physiology? List and briefly describe the general functions of the cell membrane. 3.6 Membrane proteins are classified in four categories. Describe each. 3.7 Describe the three families of cytoplasmic protein fibers. (Table 3- 2) Give examples of each. 3.8 What are the two general purposes of the insoluble protein fibers of the cell? 3.9 What is a motor protein? 3.10 Name the major organelles and inclusion of a cell. (Fig. 3- 4) 3.11 Name and describe the four primary tissue types (Table 3.4). 3.12 How are individual cells within tissues connected to each other? (Fig. 3- 8) 3.13 Describe the structure and function of gap junctions. Where in the body are you likely to find gap junctions? 3.14 Describe the structure and function of tight junctions. Where in the body are you likely to find tight junctions? 3.15 Name, describe the distinguishing characteristics of, and give the major functions of: – 5 different (functional) types of epithelia – 7 different types of connective tissue – 3 types of muscle tissue – two types of neural tissue 3.16 What is the basal lamina, and what is its function? 3.17 What distinguishes endocrine from exocrine glands? CHAPTER 3 VOCABULARY abdomen cytoplasm interstitial fluid abdominopelvic cavity cytoskeleton intracellular fluid (ICF) actin cytosol ligaments adipose tissue diaphragm lumen atrophy ducted vs ductless gland matrix basal lamina (basement elastin membrane membrane) endocrine glands microvilli calcified endoplasmic reticulum or ER mitochondria cartilage epidermis mucous membranes cell adhesion molecules or extracellular fluid (ECF) neurons CAMs extracellular matrix peritoneum cell junctions fluid mosaic model plasma cell membrane gland ribosomes cell organelles glial cells secretion cilia goblet cells tendons collagen Golgi complex thoracic cavity or thorax compartmentation ground substance tight junctions connective tissues hormones vesicles cranial cavity transmembrane proteins 6 REVIEW: CHAPTER 4 READING QUESTIONS 4.1 Understand the following terms: free energy exergonic endergonic activation energy metabolism anabolism catabolism 4.2. What is oxidative phosphorylation? 4.3. What are the starting and ending molecules in glycolysis? 4.4 What are the products of the citric acid (TCA, Krebs) cycle? 4.5. What enters and what leaves the electron transport system? 4.6. Explain the law of mass action and how the Keq of a reaction relates to it. 7 CHAPTER 5 READING QUESTIONS Background from Chapter 16 (read pp. 545 - 547) 16.1. How many liters of blood does a 70 kg man have? What percentage of his body weight does this comprise? 16.2 Describe the composition of plasma and compare it with interstitial fluid. 16.3 Where are most plasma proteins made? 16.4 Name four main groups of plasma proteins and give their functions (Table 16.1). 16.5 List the three main cellular elements of the blood and describe their primary function(s). Chapter 5 5.1 Are the body compartments in equilibrium? Explain. 5.2 Are all fluids liquids? Explain. 5.3 What is bulk flow? 5.4 Name the general properties of simple diffusion. (Table 5- 6) 5.5 When diffusion takes place across a membrane, what additional factors influence rate? (Table 5.6 and Fig 5.7) 5.6 The permeability of a membrane to a molecule depends on what 3 factors? 5.7 List the 4 functions (categories) of membrane proteins. (Fig. 5.8) 5.8 Distinguish between: a) facilitated diffusion, mediated transport, active transport b) channels, carriers, transport proteins c) water pores and ion channels d) open channels and gated channels e) cotransport, uniport, symport, and antiport f) primary, secondary, direct, and indirect active transport g) endocytosis, potocytosis, exocytosis, transcytosis, and vesicular transport h) paracellular and transcellular transport i) absorption and secretion across an epithelium j) osmolarity and tonicity 5.12 Name three categories of gated channels. 5.13 Explain how an indirect active transporter moves one molecule against its gradient. (Fig. 5.16) 5.14 Explain specificity, competition, and saturation in the context of protein- mediated processes (enzymes, receptors, transporters). 5.15 What do the following acronyms or abbreviations represent? GLUT, SGLT, ATPase, NKCC, OsM, mV, VM 5.16 Draw and label secondary active transport of glucose across an epithelium. (Fig. 5.21) 8 MEMBRANE AND EPITHELIAL TRANSPORT PROBLEMS (CHAPTER 5) 1. Which of the following means of membrane movement a) simple diffusion b) facilitated diffusion c) primary active transport d) endocytosis e) exocytosis f) secondary active transport are concentration- dependent? _______________________________________________________________ require ATP? ___________________________________________________________________________ require some input of energy other than molecular motion? _______________________________________ can be saturated? _________________________________________________________________________ require a membrane protein? _______________________________________________________________ will show competition? ____________________________________________________________________ are associated with membrane vesicles? ______________________________________________________ have rate dependent on membrane surface area? ________________________________________________ 2. Match the items in column 1 with the means by which they are most likely to be transported (column 2). In column 3, write the ONE letter that best corresponds to your rationale for selecting the means of transport. If you do not see a rationale that fits, you may write in your own rationale. Column 2: Means of transport: 1 - simple diffusion 2 - facilitated diffusion 3 - movement through a water- filled channel 4 - active transport 5 - endocytosis 6 – exocytosis Column 3: Rationale for transport: A - is polar molecule B - is nonpolar molecule C - is an ion D - is small E - is not an ion F - moving down concentration gradient G - moving against concentration gradient H - following electrochemical gradient 9 Column 1: Movement of ... Ca2+ from ECF into cells K+ from ECF into cells steroid hormone out of endocrine cell Column 2 - Moves by Column 3 - Why? 3. Match the transporter with all the descriptions that apply. __________ Na+- K+- ATPase A. symport E. secondary active transport __________ Na+- glucose transporter B. antiport F. facilitated diffusion __________ Ca2+- ATPase C. active transport __________ GLUT transporter D. cotransport 4. You are studying glucose transport across rat intestine, a process identical to that we discussed in lecture. In this protocol, you take a piece of intestine and stretch it in a ring held between two chambers. Each chamber is filled with a physiological solution whose composition can be varied. The normal physiological saline contains Na, K, Cl and other ions whose concentrations approximate that of the normal ECF. Assume that all solutions are isosmotic and that there are no effects due to osmotic movement of water. An example of the setup looks like this: In the first experiment, you place a normal physiological saline solution on the basolateral side, and a saline solution that is supplemented with glucose on the apical side. You measure the rate of appearance of glucose in the basolateral solution. This is your control experiment. In the next series of experiments, you substitute choline chloride for NaCl. Choline is a large organic cation that does not bind to transport proteins. a) What happens to glucose transport when choline chloride replaces NaCl on the apical side and why? b) What happens to glucose transport when choline chloride replaces NaCl on the basolateral side and why? c) What happens to the resting membrane potential of this cell when choline chloride replaces NaCl on the basolateral side? 5. Several lung conditions specifically affect the alveoli. For example, emphysema is a disease in which the alveoli deteriorate so that alveolar clusters look like shapeless blobs rather than the characteristic 10 grape cluster appearance. In fibrosis of the lung, scar tissue thickens the alveolar walls. Why is there impaired diffusion of oxygen from the alveolar lumen into the blood in: a. emphysema? b. fibrosis? ICF [glucose] 25 20 15 10 5 0 1 5 10 15 20 ECF [glucose] 6. In the above graph, is glucose moving into the cell by: (circle the best answer) a) simple diffusion b) active protein- mediated transport c) passive protein- mediated transport d) cannot tell from the information given Does the above graph represent saturation of glucose transport? 7. The following figure represents a section of intestinal epithelium. The black boxes represent tight junctions. Label the apical and basal sides of the epithelium. What category of epithelium does this represent? 8. Iron moves from the digestive tract as an ion, Fe++ and does so more efficiently when the pH in the digestive tract is somewhat acidic. Given the following transporters, design a cell, using the figure in 7, that could transport iron from the lumen to the blood (ECF). Show the location of the transporters and the direction of movement of the ions involved. The movement of iron from the lumen to the ECF is called _______________. H+ - Fe++ symporter H+ - Na+ antiporter Fe++ transporter (ferroportin) Na+- K+ ATPase 11 9. Prolactin stimulates milk production by the mammary glands of the breast. A mammary gland is composed of about 20 milk- secreting lobules, each made of branching ducts lined by a secretory epithelium. A major part of milk production is epithelial cell secretion of calcium from the plasma into the duct. Assume [Ca2+] in duct is same as in ECF, and the cell does NOT concentrate calcium. a. On which membrane would you expect to find Ca2+ ATPases? Circle one: apical basolateral b. On which membrane would you expect to Duct find Ca2+ channels? Circle one: apical basolateral Duct ECF c. Give the rationale for placement of the channel on this membrane: Mammary Epithelial Cell d. These cells also have Na+/K+ ATPase and Na+- dependent 2o active transport. Ca2+ can be transported out of the cell via a Na+/Ca2+ antiporter. On which membrane would you find this transporter, according to the Ca2+ - secreting function of this cell? e. How do epithelial cells establish and maintain polarity? Establish: Maintain: 12 SOLUTIONS, OSMOLARITY AND TONICITY Amount vs. concentration careful! Concentration = amount/volume To review molar solutions, per cent solutions (weight/volume), and equivalents, see p. 35- 36 of the text. The periodic table of the elements is inside the back cover of the book. ABBREVIATIONS: mol = mole M = moles/liter osmol = osmoles mosmol = milliosmoles OsM = osmoles/liter mOsM = milliosmoles/liter Atomic weights: Na 23.0, K 39.1, Cl 35.5, O 16.0, H 1.0, C 12.0. ✔ How do you make up 300 mL of a 0.9% NaCl solution? Up to this point, we have assumed complete dissociation for solutes that ionize in solution. However, the actual dissociation factor for NaCl is 1.8 - - - - at body temperature, each mole of NaCl dissociates into 1.8 moles of particles. ✔ Calculate the osmolarity of 300 mL of a 0.9% NaCl solution. The dissociation factor for NaCl is 1.8 osmoles/mole and the atomic weights are Na = 23 and Cl = 35.5. ✔ Using the dissociation factor, calculate the actual osmolarity of 5% dextrose in 0.45% saline. Osmolarity = ___________________________ 13 OSMOLARITY versus TONICITY Understanding the difference between osmolarity and tonicity is critical to making good clinical decisions about intravenous (IV) fluid therapy. The choice of IV fluid depends on how the clinician wants the solutes and water to distribute between the extracellular and intracellular fluid compartments. If the problem is dehydrated cells, the cells need fluid and the appropriate IV solution is hypotonic. If the situation requires fluid that remains in the extracellular fluid to replace blood loss, an isotonic IV solution is used. In medicine, the tonicity of a solution is usually the important consideration. ☞༅ Before trying to work the osmolarity and tonicity problems in this workbook, read pp 134- 139 in your text. Here are the rules for predicting tonicity: 1. If the cell has a higher concentration of nonpenetrating solutes than the solution, there will be net movement of water into the cell. The cell swells, and the solution is hypotonic. 2. If the cell has a lower concentration of nonpenetrating solutes than the solution, there will be net movement of water out of the cell. The cell shrinks, and the solution is hypertonic. 3. If the concentrations of nonpenetrating solutes are the same in the cell and the solution, there will be no net movement of water at equilibrium. The solution is isotonic to the cell. Fill in the following table: Hyposmotic Isosmotic Hyperosmotic ✔ ✔ ✔ Hypotonic ✔ Isotonic ✔ Hypertonic . Solving osmolarity and tonicity problems: Use the equation solute/volume = concentration (S/V = C) to mathematically determine changes to volumes and osmolarity. Concentration is osmolarity. Always begin by defining the starting conditions. This may be the person’s normal state or it may be the altered state that you are trying to return to normal. An example of this would be trying to restore normal volume and osmolarity in a person who has become dehydrated through sweat loss. You will learn to show the starting conditions for the 3- liter body both as a box diagram and in a table. The table format allows you to deal with an example mathematically if you know the volumes of the body and of the solution added or lost. 14 The body’s volumes and concentration will change as the result of adding or losing solutes, water, or both. You learned this principle as the law of mass balance. Additions to the body normally come through the ingestion of food and drink but in medical situations, solutions can be added directly to the ECF through the use of intravenous (IV) infusions. Significant solute and water loss may occur with sweating, vomiting and diarrhea, or blood loss. Once you have defined the starting conditions, you add or subtract volume and solutes to find the body’s new osmolarity. The final step is to determine whether the ECF and ICF volumes will change as a result of the water and solute gain or loss. In this last step, you must separate the added solutes into penetrating solutes and nonpenetrating solutes. For the purposes of our examples we will use three solutes: NaCl, urea, and glucose. NaCl is considered nonpenetrating. Any NaCl added to the body will remain in the ECF. Urea is freely penetrating and behaves as if the cell membranes dividing the ECF and ICF do not exist. An added load of urea will distribute itself until the urea concentration is the same throughout the body. Glucose (also called dextrose) is an unusual solute. Like all solutes, it first goes into the ECF but over time, 100% of added glucose will enter the cells. When glucose enters the cells, it is phosphorylated to glucose 6- phosphate (G- 6- P) and cannot leave the cell again. So although glucose enters cells, it is not freely penetrating because it stays in the cell and adds to the cell’s nonpenetrating solutes. Giving someone a glucose solution is the same as giving them a slow infusion of pure water because glucose 6- phosphate is the first step in the aerobic metabolism of glucose. The end products of aerobic glucose metabolism are CO2 and water. OSMOLARITY AND TONICITY PROBLEMS The examples shown in below walk you through the process of adding and subtracting solutions to the body. Ask the following questions when you are evaluating the effects of a solution on the body I. What is the osmolarity of this solution relative to the body? II. What is the tonicity of this solution? (Use the table above (SG p 15) to help eliminate possibilities.) To determine tonicity, compare the concentration of the nonpenetrating solutes in the solution to the body concentration. (All starting body solutes are considered to be nonpenetrating.) For example, consider a solution that is 300 mOsM – isosmotic to a body that is 300 mOsM. The solution’s tonicity will depend on the concentration of nonpenetrating solutes in the solution. If the solution is 300 mOsM NaCl, the solution’s nonpenetrating solute concentration is equal to that of the body. When the solution mixes with the ECF, the ECF nonpenetrating concentration and osmolarity do not change. No water will enter or leave the cells (the ICF compartment), and the solution is isotonic. Now suppose the 300 mOsM solution has urea as its only solute. Urea is a penetrating solute, so this solution has zero nonpenetrating solutes. When the 300 mOsM urea solution mixes with the ECF, the added volume of the urea solution dilutes the nonpenetrating solutes of the ECF. (S/V = C. The same amount of NP solute in a larger volume means a lower NP concentration.) Now the nonpenetrating concentration of the ECF is now less than 300 mOsM. The cells still have a nonpenetrating solute concentration of 300 mOsM, so water moves into the cells to equalize the nonpenetrating concentrations (Rule: water moves into the compartment with the higher 15 concentration of NP solutes). The cells gain water and volume. This means the urea solution is hypotonic, even though it was isosmotic. Example 2 below shows how combining penetrating and nonpenetrating solutes can complicate the situation. This example asks you to describe the solution’s osmolarity and tonicity based on its composition before you do the mathematical calculations. This skill is important for clinical situations, when you will not know exact body fluid volumes for the person needing an IV. For all problems, define your starting conditions. Assume that all initial body solutes are nonpenetrating (NP) and will remain in either the ECF or ICF. Use the equation solute/volume = concentration (S/V = C) to solve the problems. You will know two of the three variables and can calculate the third. Remember that body compartments are in osmotic equilibrium. Once you know the total body’s osmolarity (concentration), you also know the ECF and ICF osmolarity because they are the same. In the tables below, the boxes with ?? indicate the unknowns that must be calculated. STARTING CONDITION: We have a 3- liter body that is 300 mOsM. The ECF is 1 liter and the ICF is 2 liters. Use S/V = C to find out how much solute is in each of the two compartments. Rearrange the equation to solve for S: S = CV. SICF = 300 mosmol/L 2 L = 600 mosmol NP solute in the ICF SECF = 300 mosmol/L 1 L = 300 mosmol NP solute in the ECF We can also do these calculations using the following table format. This table has been filled in with the values for the starting body. Remember that the ECF + ICF must always equal the total body values, and that once you know the total body osmolarity, you know the ECF and ICF osmolarity. Total Body ECF ICF S Solute (mosmoles) 900 mosmol 300 mosmol 600 mosmol V Volume (L) 3 L 1 L 2 L C Osmolarity (mOsM) 300 mOsM 300 mOsM 300 mOsM To see the effect of adding a solution or losing fluid, start with the table above and add or subtract volume and solute as appropriate. You cannot add and subtract concentrations. You must use volumes and solute amounts. 16 1. Work the total body column first, adding or subtracting solutes and volume. 2. Once you calculate the new total body osmolarity, carry that number across the bottom row to the ECF and ICF columns. (The compartments are in osmotic equilibrium.) 3. Distribute nonpenetrating solutes to the appropriate compartment. NaCl stays in the ECF. Glucose goes into the cells. 4. Use V = S/C to calculate the new compartment volumes. EXAMPLE 1: Add an IV solution of 1 liter of 300 mOsM NaCl to this body. This solution adds 1 liter of volume and 300 mosmoles of NaCl. Total Body S- Solute (mosmoles) 900 + 300 = 1200 osmoles V- Volume (L) 3 + 1 = 4 L C- Osmolarity (mOsM) 1200/ 4 = 300 mOsM Work total body first. Add solute and volume, then calculate new osmolarity (bold- italics). Carry the new osmolarity across to the ECF and ICF boxes (arrows). All of the added NaCl will stay in the ECF, so add that solute amount to the ECF box. ICF solute amount is unchanged. Use V = S/C to calculate the new ECF and ICF volumes (bold- italics). Total Body ECF ICF S (mosmol) 1200 mosmol 300 + 300 = 600 600 V (L) 4 L 2 L 2 L C (mOsM) 300 mOsM ➔ 300 mOsM ➔ 300 mOsM The added solution was isosmotic (300 mOsM) and its nonpenetrating concentration was the same as that of the body’s (300 mOsM NP). You would predict that the solution was isotonic, and that is confirmed with these calculations, which show no water entering or leaving the cells (no change in ICF volume). EXAMPLE 2: Add 2 liters of a 500 mOsM solution. The solution is equal parts NaCl (nonpenetrating) and urea (penetrating), so it has 250 mosmol/L NaCl and 250 mosmol/L urea. This solution has both penetrating and nonpenetrating solutes, but only nonpenetrating solutes contribute to tonicity and cause water to shift between compartments. Before working this problem, answer the following questions: (a) This solution is __________osmotic to the 300 mOsM body. (b) What is the concentration of nonpenetrating solutes [NP] in the solution? _______________ (c) What is the [NP] in the body? ________ (d) Using the rules for tonicity, will there be water movement into or out of the cells? If so, in which direction? (e) Based on your answer in (d), this solution is ________tonic to this body’s cells. 17 Now work the problem using the starting conditions table as your starting point. What did you add? 2 L of (250 mosmol/L urea and 250 mosmol/L NaCl) = 2 liters of volume + 500 mosmol urea + 500 mosmol NaCl. Urea does not contribute to tonicity, so we will set the 500 mosmol of urea aside and only add the volume and NaCl in the first step: Step 1: Add 2 liters and 500 mosmoles NaCl. Do total body column first. Total Body S (mosmol) 900 + 500 = 1400 mosmol V (L) 3 + 2 = 5 L C (mOsM) 1400/5 = 280 mOsM Step 2: Carry the new osmolarity across to ECF and ICF. NaCl all remains in the ECF so add that solute to the ECF column. Calculate new ECF and ICF volumes. Total Body ECF ICF S (mosmol) 1400 mosmol 300 + 500 = 800 600 V (L) 5 L 2.857 L 2.143 L C (mOsM) 280 mOsM ➔ 280 mOsM ➔ 280 mOsM Notice that ECF volume + ICF volume = total body volume. Step 3: Now add the reserved urea solute to the whole body solute to get the final osmolarity. That osmolarity carries over to the ECF and ICF compartments. Urea will distribute itself throughout the body until its concentration everywhere is equal, but it will not cause any water shift between ECF and ICF, so the ECF and ICF volumes remain as they were in Step 2. Total Body ECF ICF S (mosmol) 1400 + 500 = 1900 V (L) 5 L 2.857 L 2 .143 L C (mOsM) 1900/5 = 380 mOsM ➔ 380 mOsM ➔ 380 mOsM Answer the following questions using the values in the table: (f) What happened to the body osmolarity after adding the solution? _____________ This result means the added solution was ___________osmotic to the body’s starting osmolarity. (g) What happened to the ICF volume? ________________________ This means the added solution was ____________tonic to the cells. Compare your answers in (f) and (g) to your answers for (a)- (e). Do they match? They should. 18 If you know the starting conditions of the body and you know the composition of a solution you are adding, you should be able to describe the solution’s osmolarity and tonicity relative to the body by asking the questions in (a)- (e). Summary: Working Human Subject Problems General tips on osmolarity & tonicity problems: Solutes NaCl—functionally non- penetrating; will not enter cells Urea—freely penetrating, moving back and forth between ECF and ICF until [urea] equal. (i.e. when concentration, not amounts, are equal!) Glucose (dextrose) –penetrates cell but once inside is phosphorylated and becomes non- penetrating (i.e. adds to the intracellular concentration of non- penetrating solutes). Intracellular solutes—non- penetrating Water • Water will distribute based on the relative concentrations of the nonpenetrating solutes. Water moves to the compartment with the higher concentration of nonpenetrating solutes. • Water distributes evenly across all compartments, so at equilibrium: ECF osmolarity = ICF osmolarity = total body osmolarity • All administered fluids go first into the ECF. • Any time you add a volume to a body, the volume of the total body (and therefore of at least one of its compartments) must increase. • Any time you add a solution to a body, the final osmolarity of the body will depend on the osmolarity of the added solution. • Any time you add solute only (e.g., eat salt), the body osmolarity will increase. Rules Always deal with total body volume, solutes, and osmolarity first. ECF and ICF osmolarity will ALWAYS be the same as total body osmolarity. (Why?) 19 Useful Protocol for solving Human Subject Problems Separate the added solution into three components: water, penetrating solutes, and nonpenetrating solutes: Test your understanding by working the example problems that follow. Example #1: Assume a total body volume of 3 L, with 1 L in the ECF and 2 L in the ICF. ECF = 1 L ICF = 2 L There are no solutes in either compartment. Add 6 particles of urea to the ECF and allow the system to go to equilibrium. How will the urea be distributed? Draw "o"s in each box to represent the urea particles at equilibrium. How many urea particles will be in the ECF? _______ in the ICF? ______ What is the concentration of urea in the ECF in particles/L? ________ in the ICF? ___________ Is your system at equilibrium? If not, change it until it is. Notice that to "distribute the urea evenly" you did not put half into each compartment. The amount that goes into each compartment is based on the VOLUME of the compartment. Example #2: You administer an IV with 3 liters of 50 mM NaCl to a person whose osmolarity is 300 mOsM and whose total body water is 30 L. Assume one- third of total body water is in the ECF. Assume complete dissociation. Using the information above, fill in the following blanks that represent the information you need to solve the problem: 20 Starting body conditions: Osmolarity = ____________________. Total body water = ____________ L. ECF volume = ____________ L. ICF volume = _______________ L. Volume of fluid administered = __________ L. Total amount of solute administered = ___________ mosmoles. *Note that you need to change the solution from moles to osmoles!! ☛ Step 1: Make a chart with starting values. Volumes and osmolarity are usually given. From those values, calculate starting solute amounts. (solute/volume = osmolarity) * Always do total body first. Chart 1 Starting values Total* ECF ICF Solute Volume Concentration ☛ Step 2: Make another chart that adds water and nonpenetrating solutes. Mentally set any penetrating solute amount to the side – you will add them back in the last step. Chart 2: Starting values + solution volume + nonpenetrating solutes Total ECF ICF Solute Volume Concentration For each solute added, you must do the following: ☛ Figure out the total amount of solute added (in osmoles or milliosmoles) ☛ Decide how the solute will distribute between ECF and ICF. ☛ Always start calculations with total body values: Starting total body volume + total added volume = final total body volume Starting total body solutes (osmoles) + total added solutes = final total body solutes Total body osmolarity will be the same for all body compartments at equilibrium!!! In this example, you did not need to use step 3 because there were no penetrating solutes. Example #3: The same person from the previous problem instead is given 1 liter of an IV contained 250 mOsM NaCl and 50 mOsM urea. 21 To work this, make three charts. Chart 1 is the starting values chart. Chart 2 adds nonpenetrating solutes and water and takes the system to equilibrium. Chart 3 adds the penetrating solutes and distributes them proportionately according to the relative volumes of the ECF and ICF as determined in chart 2. Chart 1: Starting values Starting values Total ECF ICF Solute Volume Concentration Chart 2: Add volume and nonpenetrating solutes only Total ECF ICF Solute Volume Concentration Addition of the penetrating solutes will change the osmolarity but not the compartment volumes!! Chart 3: Add penetrating solutes Total ECF ICF Solute Volume Concentration 22 How much volume in the ECF and the ICF? Determining Volumes of Distribution To determine the volumes of the body compartments, we can use dilution techniques in which a known amount of a marker in a known volume is given to the subject. The marker is allowed to distribute and then a sample of the compartment liquid is removed and analyzed for the concentration of the marker. Because the concentration of the marker in the sample is the same as the concentration throughout the compartment, the following ratio can be used to calculate compartment volume: Amount of marker in sample (known) = total amount of amount of marker (known) Volume of sample (known) total volume of compartment (unknown) For example, 1 gram of dye is put into a vat of water. The dye is stirred until it is evenly distributed throughout the vat. A mL sample of water is found to contain 0.02 mg of dye. What is the volume of the vat? 0.02 mg dye/1 mL = 1000 mg dye/ X mL X=1000 mg dye*1 mL/0.02 mg dye X = 50,000 mL or 50 L The determination of body compartment volumes in humans has been done using various markers that are restricted to the compartment being measured physiologically. For example, total body water (TBW) has been estimated using water with radioactive isotopes of hydrogen (either deuterium oxide D2O or tritium oxide). Inulin or sucrose can be used to measure ECF volume. Evans blue, a dye, is used to measure plasma volume. There are no markers for the interstitial fluid and the intracellular compartments, but we can calculate or estimate those volumes. How? 23 Single cell tonicity problems: a single red blood cell in an infinite volume of solution If you are given detailed information, as in the problems above, you can always ‘plug and chug’ the numbers. But suppose you have a person who comes in the ER and needs an IV for dehydration. To make the appropriate decision, you must know how any given IV solution affects the body’s osmolarity and its cell volumes (i.e., the tonicity of the solution). We will use RBC problems to learn this skill. You have two compartments: the cell (RBC) and the solution in which it is placed. The volume and concentration of the solution will never change measurably. Determine the parameters using these guidelines: Osmolarity of solution vs. cell Compare cell and solution before cell is placed in the solution. Tonicity of the solution Determine cell volume after cell is placed in the solution and equilibrated. Graph of volume change vs. time Shows what occurs when cell is placed in the solution. The starting osmolarities of the cell and solution don't make any difference in determining tonicity. Neither does the presence of penetrating solutes because they will move freely into the cell as if the membrane doesn't exist. 1 2 Solution is ________osmotic Solution is _________osmotic and __________tonic. and tonic. 24 3 4 300 mOsM NP solutes 300 mOsM NP solutes 3 00 mOsM u rea 200 mOsM urea The solution is ____________osmotic. The solution is ____________osmotic. The solution is ____________tonic. The solution is ____________tonic. Now let’s try some solutions with mixtures of solutes. 5 6 300 mOsM NP solutes 300 mOsM NP solutes 3 00 mOsM NaCl + 3 00 mOsM u rea 200 mOsM NaCl + 200 mOsM urea The solution is ____________osmotic. The solution is ____________osmotic. The solution is ____________tonic. The solution is ____________tonic 25 7 8 The solution is ____________osmotic. The solution is ____________osmotic. The solution is ____________tonic. The solution is ____________tonic. 26 SOLUTIONS, OSMOLARITY, AND TONICITY PRACTICE PROBLEMS Use 1.8 for NaCl dissociation. Atomic weights: Na 23.0, K 39.1, Cl 35.5, O 16.0, H 1.0, C 12.0. 1. How do you make up 200 mL of a 5% dextrose (= glucose, C6H12O6) solution? 2. How do you make up 300 mL of a 0.9% NaCl solution? 3. If you mix two liters of 1 M NaCl with one liter of 3 M glucose: What is the total concentration of the resulting solution? ______________________ What is the concentration of NaCl in M? __________ in OsM? ___________ What is the concentration of glucose in M? ____________ and OsM? _______________ 4. Calculate the osmolarity of 300 mL of a 0.9% NaCl solution if the dissociation constant for NaCl is 1.8 osmoles/mole and the atomic weights are Na = 23 and Cl = 35.5. 5. Calculate the actual osmolarity of 5% dextrose in 0.45% saline (using dissociation constant = 1.8) Osmolarity = ___________________________ 6. What happens to a red blood cell with internal osmolarity of 300 mOsM when it is placed in the following solutions? a) 600 mOsM NaCl _____________________ b) 600 mOsM urea _________________________ c) 300 mOsM urea/ 400 mOsM NaCl _______________________________ 7. What - osmotic and - tonic are the solutions relative to the cell? a) 600 mOsM NaCl is _________________osmotic and _____________________tonic to the cell. b) 600 mOsM urea is ___________________osmotic and ____________________tonic to the cell. c) 300 mOsM urea/300 mOsM NaCl is ______________osmotic and _________________tonic to the cell. 27 8. You are doing an experiment on how a new drug distributes in the human body. For subject #134, a woman, you have determined a deuterium oxide (D2O) volume of 27.0 L. You have inulin in a concentration of 5 mg/ml. You administer 1 ml of this solution to subject #134 by IV (intravenously). It is not metabolized or excreted and distributes evenly within 10 minutes. You withdraw a blood sample which has 2 ml of plasma. You analyze the plasma sample and find an inulin content of 0.001 mg. What is subject #134's interstitial volume? What is her intracellular fluid volume? 9. TRUE/FALSE/Explain Limit explanations to maximum 3 sentences. A solution that is hyposmotic to a cell can be either hypotonic or isotonic to the same cell, depending on the nature of the particles in question. Circle one: True False Explanation? 10. What happens to the following parameters (at equilibrium) when the following solutions are administered by IV to patients whose body osmolarity is 300 mOsM? 300 mOsM NaCl and 300 mOsM urea What happens to ICF volume? What happens to ICF osmolarity? What happens to ECF volume? What happens to ECF osmolarity? 11. A patient has a plasma osmolarity of 300 mOsM. Using arrows or nc (no change) indicate whether ECF and ICF parameters will increase, decrease or remain the same under the circumstances given. Assume that LiCl behaves the same as NaCl, and that instantaneous equilibration occurs. 6 pt ECF volume ECF osmolarity ICF volume ICF osmolarity Ingest 1.5 grams of LiCl Administered IV of 300 mOsM LiCl + 50 mOsM urea 12. For the question below, use this information: Normal body osmolarity is 300 mOsM. Normal total body water is 60% of total body weight. Normal ECF volume is half of ICF volume. Assume all solute loss comes from the ECF. In the first Gulf war, you are an Army medic. Operation Desert Storm has continued into the summer months, and dehydration is a real problem with the ground troops who are cut off from their supplies. One of your troops brings in an Iraqi soldier who was found unconscious in the desert after his patrol 28 ran out of water. Through an interpreter you learn from his buddy that he normally weighs 70 kg. His current weight is 64 kg, his plasma osmolarity is 332 mOsM, and he has dry mucous membranes and other physical signs of dehydration. You know that you need to start intravenous fluid replacement in this man, but your IV supplies have run out. You do have sterile distilled water and a bottle of sodium chloride which you can use to make your own IV fluid, but even that is running low. From the information given, calculate the volume and osmolarity of a sodium chloride solution that will EXACTLY replace the soldier's fluid loss and return him to normal volume and osmolarity. a) The solution you want to make up will be: (circle the best answer) a) isomotic and isotonic b) hyperosmotic and hypotonic c) hyposmotic and isotonic d) isomotic and hypotonic e) hyposmotic and hypotonic d) hyperosmotic and hypertonic b) The replacement solution will be _____________ (vol) and have a concentration of ____________________. 29 Discussion Exercise: More Fun with Osmolarity and Tonicity Sandra eats compulsively when nervous. While studying one evening, she consumed several bags of pretzels. After digestion and absorption of the salt, the net effect was ingestion of 4 g of NaCl. Sandra’s normal statistics: weight: 135 lb D2O volume: 55% of weight plasma [Na+]: 130 mM inulin volume: 11.0 L plasma osmolarity: 305 mOsM 1. What was the effect of ingestion of NaCl on the following parameters? Use arrows for increase & decrease, and nc for no change. Assume equilibration has occurred. ECF vol ECF osmolarity ICF volume ICF osmolarity 2. For the following, use dissociation constant = 2 for NaCl. Use units and round as shown. a) What was her ICF volume before salt consumption? Answer: L b) How many osmoles of NaCl did she ingest? Answer: osmol c) What was her ICF solute after salt consumption? Answer: osmol d) What was her final ICF osmolarity? Answer: mOsM Use the charts to help you answer the questions. Start Total ECF ICF + NaCl Total ECF ICF Vol 0.1L Vol 0.1 L Sol 0.001 osmol mOsM Sol 0.001 osmol mOsM 3. How many liters of pure water would Sandra need to drink in order to return her plasma osmolarity to 305 mOsM? Answer: L 4. How might drinking a liter of D5W benefit Sandra (after ingestion of NaCl)? Use the chart below to help you explain. + D5W Total ECF ICF Vol 0.1 L Sol 0.001 osmol mOsM 30 5. An RBC with an internal concentration of 290 mOsM non- penetrating is in a solution consisting of 320 mOsM NaCl and 50 mOsM urea. a) At the first arrow on the graph, the RBC is taken from that solution and placed in a solution of 290 mOsM NaCl and 150 urea. Draw a line on the graph between the arrows to show what happens to cell volume. Cell volume Time At the 2nd arrow, the cell is removed from the solution in #1and placed in distilled water. Explain what happens to the cell as briefly as possible. 6. Make a chart comparing and contrasting standard IV solutions. Think of other points of comparison Solution Osmolarity Osmolarity Tonicity compared to body = compared to 300 mOsM body cells (300 mOsM) 31 CHAPTER 6 READING QUESTIONS 6.1. Why do some cells respond to a chemical signal while other cells ignore it? (Fig. 6.1) 6.2 What kinds of signals pass through gap junctions? 6.3 Distinguish between the following pairs or groups: a) first and second messengers b) up- regulation and down- regulation c) lipophobic and lipophilic messengers d) neurotransmitter, neuromodulator, and neurohormone e) cytokine and peptide hormone8 f) lipophobic and lipophilic signal molecules, their receptors and actions g) autocrine, paracrine, neurocrine, and endocrine signals 6.4 List the 4 major categories of cell membrane receptors. (Fig. 6.3) 6.5 What are signal transduction and signal amplification? (Fig. 6.4 and 6.5) 6.6 List five major 2nd messengers. (Fig 6.6C) 6.7 How do G proteins function in signal transduction? (Fig 6.8, 6.9) 6.8 How does extracellular calcium enter the cell? Where and how is intracellular calcium stored? (Fig. 6.11) 6.9 Why do many signal receptors exhibit specificity, competition, and saturation? 6.10 What are the three components of a physiological control system in its simplest form? (Fig. 1.7) 6.11 What is tonic control? 6.12 What are two control systems are involved with long- distance pathways? Name the third body system that plays a key role in long- distance communication. 6.13 List the components of a reflex pathway in order. (Fig. 6.16) 6.14 What is the role of a CNS or endocrine integrating center? 6.15 What is the purpose of a feedback loop? 6.16 Distinguish between the following pairs or groups: a) central and peripheral receptors b) local and long- distance control c) agonists and antagonists d) positive and negative feedback and feedforward control e) tonic and antagonistic control 6.17 Compare and contrast neural and endocrine control systems on the basis of five key areas that follow (Table 6.2): Specificity Nature of the Signal (Fig. 6- 31) Speed Duration of Action Coding for Stimulus Intensity CHAPTER 7 READING QUESTIONS 7.1 Define a hormone. 7.2 List 3 possible ways hormones act on their target cells 7.3 List the four classic steps for identifying an endocrine gland. 7.4 What is meant by cellular mechanism of action? 7.5 What determines the variable responsiveness of cells to a particular hormone? 7.6 What is the half- life of a hormone? What generally happens to hormones in the bloodstream? 32 7.7 List three chemical classes of hormones. For each class, be able to tell how it is made in the endocrine cell, timing of synthesis and release, how released from endocrine cell, how transported in blood, where target cell receptors are located, and general type of cellular response. (Tbl. 7.1) 7.8 Explain the differences between preprohormone, prohormone, and hormone. Where is each made? (Fig. 7.3) 7.9 Name some of the post- translational modifications a prohormone can undergo. (Review post- translational modification in Chapter 4) 7.10 Name 5 tissues that make steroid hormones and the 6 major steroid hormones (some are groups of related hormones). (Fig. 7.2) 7.11 Name 3 tissues that make amino- acid- derived hormones and the 6 major hormones. (Fig. 7.2) 7.12 Describe the components of a simple endocrine reflex. What serves as the sensor? The integrating center? (Use insulin or parathyroid hormone as your exemplar.) Describe the feedback loop in this system. (Fig. 7.7) 7.13 Where are posterior pituitary hormones made, and how do they get to the posterior pituitary? How does this process differ from the synthesis- storage- release pattern followed by traditional peptide hormones? (Fig. 7.8) 7.14 Describe the components of an endocrine reflex that is mediated by hypothalamic releasing or inhibiting hormones. What serves as the sensor? The integrating center? Describe the feedback loop in this system. (Fig. 7.11a) 7.15 How does negative feedback in the hypothalamic- pituitary pathway differ from previously described patterns of negative feedback? (Fig7.11) 7.16 Distinguish between long- loop negative feedback and short- loop negative feedback. Give examples of each. (Fig. 7.11) 7.17 Describe or diagram the structure of a portal system. Name the locations of three portal systems in the body. What is the primary advantage of using a portal system? (Fig. 7.8b) 7.18 For the following hormones, be able to draw the normal control pathway for their release: cortisol, thyroid hormone, parathyroid hormone, insulin, growth hormone. (Fig. 7.7, 7.10, 7- 11c) 7.19 Distinguish between a) permissiveness and synergism b) anterior and posterior pituitary c) control pathways for anterior and posterior pituitary hormones 7.20 List the three basic patterns of endocrine pathology: 7.21 What is the difference between a primary endocrine pathology and a secondary endocrine pathology? Give an example of each. (Fig. 7.14) ✔ If the effect of a hormone is not measurable until 30- 90 minutes after the hormone is applied, what would you assume is the cellular action of the hormone? ____________________________________________________________________________________ ✔ If the effects of a hormone are rapid and can be measured in seconds to a few minutes, what would you assume is the cellular action of the hormone? ✔ Fill in the table below with the three major tissues that release neurohormones. Are the neurohormones synthesized in that tissue or elsewhere? 33 Location Site of release Site of synthesis 1 2 3 ✔ What is meant by nongenomic effects of steroid hormones? ✔ With which pathology pattern would you be most likely to find down- regulation of receptors in the target tissues? Explain. ✔ Lactation is under the influence of prolactin from anterior pituitary. Where in/on the target cell would you expect to find the prolactin receptor? 34 SIGNALING AND ENDOCRINE CONTROL PROBLEMS (CHAPTERS 6 & 7) 1. Name the parts of a general reflex (stimulus, etc.) in the left column and describe the specific parts of the reflex for the PTH pathway: a decrease in plasma [Ca2+] is sensed by cells of the parathyroid gland, which secretes parathyroid hormone (PTH). PTH acts on the kidney to increase Ca2+ reabsorption and on bone to increase release of Ca2+. (you may or may not need all of the boxes provided). General steps of a reflex Corresponding part of PTH pathway 2. If a hormone has characteristic or activity listed below, fill in the blank with the appropriate letter indicating which type of hormone it would be. S= steroid P=peptide N=neither B=both ____ Ligand- receptor complex acts as transcription factor to induce synthesis of new Ca2+ channel subunits ____ Binds to the plasma protein albumin ____ Stored in cell; released upon signal ____ Synthesized on demand ____ Activates cAMP, resulting in H2O pores being placed in membrane ____ Made from tyrosine ____ Interactions include both synergism and antagonism 3. All hormones have complex and interesting interactions and regulatory actions involving other hormones. Use the symbols to appropriately describe the following interactions or feedback mechanisms. Each can be used more than once, or not at all. P = permissiveness S=synergism + = positive feedback A=antagonism N=none - = negative feedback Hormone A decreases plasma glucose by increasing uptake of glucose into cells. Hormone B increases plasma glucose by stimulating breakdown of glycogen into glucose. Hormones B,C & D each individually increase plasma glucose levels. Hormone C also downregulates receptors for hormone A (see above—decreases plasma glucose). 35 Hormone X affects certain aspects of sexual development. Hormone Z generally affects the cardiovascular and nervous systems, but also has been shown to upregulate receptors for Hormone X. Questions 4 – 11 integrate hypothalamic control, 1o vs. 2o pathologies, steroid vs. peptide hormones 4. Three patients in the waiting room of an endocrinologist’s office all have thyroid disorders. The patients, their disorders and descriptions are given below. In order to address these questions, first draw a horizontal flowchart illustrating feedback in the hypothalamic- anterior pituitary pathway. Include all organs and hormones involved. 5. Which data set below belongs to which patient? Write the correct letter in the blank by the patient’s name. Or write N if none is correct. The levels of hormone given are all endogenous levels. T4 (ng/dL) TSH (pg/mL) TRH (pg/mL) normal levels 1- 3 5- 50 10- 40 Data A 0.05 75 85 Data B 7.5 2 5 Data C 6 82 4 Data D 0.4 1 55 Data set Patient Disorder Colin rare hypersecreting hypothalamic tumor Sam iodine deficiency resulting in low production of thyroid hormone Barbara Graves’ disease—an autoimmune disease in which antibodies produced completely mimic TSH 6. Does data set D represent a primary or secondary pathology? Circle one: primary secondary Briefly explain. 7. In the hypothalamic control pathway for release of T4 (and T3), what functions as the: first integrating center final integrating center first efferent final efferent 8. The thyroid hormones T3 and T4 are synthesized while attached to thyroglobulin, a large protein. Just before release from thyroid cells, they are stripped from the thyroglobulin and become lipophilic. By what method of movement do T3 and T4 leave the thyroid cell? 36 9. Which is more likely to be an effect of T3 and T4? Circle correct answer. a. Stimulate production of Na+/K+ ATPase subunits b. Upregulate Na+ channel activity by upregulation of IP3 10. This graph depicts plasma TSH as a function of plasma levels of T4 under normal and pathological conditions. a. Which symbol represents data from a hyperthyroid condition? Circle one: circle square triangle b. Do the data (cicles) indicate primary hyperthyroidism or secondary hyperthyroidism? Circle: 1o 2o Explain. 11. Circle the correct reflex pattern by which release of T4 occurs:S=stimulus, R=receptor, Endo=endocrine gland a. Sà༎ Rà༎ CNSà༎ efferent nerveà༎ endo 1à༎ neurohormoneà༎ endo2à༎ hormoneà༎ targetà༎ response b. Sà༎Rà༎CNSà༎neurohormoneà༎endo1à༎hormoneà༎effector organà༎response c. Sà༎Rà༎CNSà༎neurohormoneà༎endo1à༎hormoneà༎endo 2à༎hormoneà༎targetà༎response d. Sà༎Rà༎endo 1à༎hormoneà༎endo 2à༎hormoneà༎effector organà༎response 37 Discussion Exercise: Hormones and Hypothalamic Control An endocrinologist examines two patients with reproductive issues. Patient A is 23 year old female who has Kallman’s syndrome, a disorder that results in hyposecretion of hypothalamic hormones. Patient B has is 55 years old and is experiencing menopausal ovarian failure. An understanding of the control pathway for reproductive hormones is central to diagnosing these pathologies. 1. Draw a flowchart illustrating hypothalamic control of reproductive hormones. 2. Use your flowchart to help you decide which reflex pattern is correct. Circle the correct reflex pattern by which release of estrogens & progesterone occurs. S=stimulus, R=receptor, Endo=endocrine gland a. Sà༎Rà༎CNSà༎efferent nerveà༎endo 1à༎neurohormoneà༎endo 2à༎hormoneà༎targetà༎response b. Sà༎Rà༎CNSà༎neurohormoneà༎endo1à༎hormoneà༎effector organà༎response c. Sà༎Rà༎CNSà༎neurohormoneà༎endo1à༎hormoneà༎endo 2à༎hormoneà༎targetà༎response d. Sà༎Rà༎endo 1à༎hormoneà༎endo 2à༎hormoneà༎effector organà༎response 3. In the neuroendocrine reflex pathway resulting in E/P release, what is: the 2nd integrating center? 2nd efferent? 4. What are the relative levels of each of the relevant hormones? Write in the other hormones under “Hormone” and the origin of the hormone under “synthesized in.” Draw arrows (↓,↑) for low or elevated under Patient A and Patient B. Synthesized Hormone(s) Patient A Patient B in: ovaries Estrogens/progesterone 5. Which patient has 1o hypogonadism? Circle one: A B both neither Briefly explain. 5. Propose an appropriate treatment for patient A. 38 NEUROPHYSIOLOGY REVIEW (CHAPTERS 8- 11) You should have learned the basics of graded and action potentials and the nervous system in Introductory Biology. Because other Biology courses focus on neurobiology, we will do only a quick overview in BIO 365S. Your reading should focus on the following: 1. Organization of the nervous system (pp. 238- 245) 2. Review of membrane potential (pp 160- 168 & 248- 251) 3. Graded potentials and action potentials (pp 251- 266) 4. Basics of synaptic transmission (pp 266- 274) and neurocrines & neurotransmitters listed in Table 8- 4) 5. Neural pathways pp 274- 280 6. Major parts and functions of the CNS summarized in Fig 9.2 through 9.5, 9.7, 9.8 (focus on diencephalon & brainstem) and 9.18. 7. Compare and contrast autonomic vs somatic divisions of the peripheral nervous system (summarized in Fig 11.5, 11.6, Table 11.1 through 11.3) Be able to answer the following end- of- chapter questions in your textbook: Ch. 8: 1- 5, 8, 11- 13, 15, 17 Ch. 9: 9, 10, 16 Ch. 11: 1, 3- 5, 15. If you need a review of resting membrane potential, see the activity posted in Blackboard that you can work through in a group or on your own. ✔ You should understand the following concepts: Resting membrane potential difference (Vm) Equilibrium potentials or Eion ✔ Draw and label a graph of membrane potential as a function of time showing: Depolarization Repolarization Hyperpolarization ✔ Distinguish between the following pairs: 1. A graded potential and an action potential (pp. 255- 272) 2. Neuron and nerve 3. Ganglion and nucleus (in the brain) ✔ (Ch. 10. Table 10.2) What kinds of sensory receptors respond to the following stimuli? a) oxygen ______________________________ b) temperature ______________________________ 39 c) osmolarity d) pressure e) glucose f) pH ______________________________ ______________________________ ______________________________ ______________________________ ✔ Map, create a table, or diagram the efferent divisions of the nervous system to distinguish them on the basis of the following: - .Location of neuron cell bodies for somatic motor, sympathetic, and parasympathetic pathways - CNS location for origin of sympathetic and parasympathetic pathways - Neurotransmitters and their receptors for targets of the different divisions. Include subtypes of receptors. - Location of ganglia for the two autonomic divisions 40 NEUROPHYSIOLOGY PROBLEMS 1. Name the neurotransmitter or neurohormone that is secreted by each of the following and name ALL the receptor types found on the targets for that particular neurotransmitter/neuron. Neuron/cell Neurotransmitter/hormone Receptor type(s) on target cell preganglionic autonomic neuron sympathetic postganglionic neuron adrenal medulla somatic motor neuron 2. Which part of the nervous system is illustrated (circle the answer that is most complete): Target Organ ACh a. somatic e. sympathetic b. autonomic f. b and c c. parasympathetic g. b, c and d d. afferent NorEpi h. b and e 3. Fill in the blanks regarding the branch of the nervous system that increases heart rate. a) preganglionic fiber: Neurotransmitter ______________ Receptor(s) ___________________ b) postganglionic fiber: Neurotransmitter ______________ Receptor(s)___________________ c) other general types of target organs: 41 4. The following statements test your knowledge of the autonomic nervous system. Fill in the blanks with the appropriate letter: P = parasympathetic, S = sympathetic, B = both para & symp, N = neither a) _____ decreases heart rate by releasing ACh onto autorhythmic cells b) _____ releases norepinephrine onto muscarinic receptors c) _____ efferent division of the nervous system d) _____ 2 neuron chain in pathway e) _____ nicotinic receptors on autonomic ganglia f) _____ releases norepinephrine onto α receptors on arteriolar smooth muscle g) _____ fight or flight reflex 5. For a typical mammalian cell, match the changes in the left column with the appropriate answer. Extracellular [K+]goes from 4 to 6 mM __________ a. membrane depolarizes Extracellular [Na+] goes from 135 to 137 mM _________ b. membrane hyperpolarizes Membrane permeability to K+ (PK) increases __________ c. resting membrane potential does not Membrane permeability to Na+ (PNa) increases_________ change significantly 6. TRUE/FALSE/Explain Limit explanations to maximum 3 sentences. Anything beyond will be disregarded If the Na+/K+-ATPase is blocked by an inhibitor such as ouabain, the membrane potential will increase and rapidly go to zero mV. Circle one: True False Explanation: 42 MUSCLE REVIEW You should have learned the basics of muscle physiology in introductory biology. Please review the following information in Chapter 12: Muscles – (p.399, Fig. 12.1, 12.3, 12.7, 12.10, 12.11, 12.23, Table. 12- 3) Use the terms in Q 21 on p. 443 of the text to make a map of skeletal muscle contraction. ✔ Compare the action potentials of a skeletal muscle to those of a neuron. Neuron Skeletal muscle fiber Resting membrane potential (mV) Stimulus to begin action potential Rising phase (ions, direction) Falling phase (ions, direction) Duration of action potential 43 44 CARDIOVASCULAR PHYSIOLOGY 14.1 Describe the basic structure of a cardiovascular (CV) system. 14.2 List at least five substances transported by the blood. (Table 14- 1) 14.3 What are the key functions of the CV system? 14.4 How do arteries differ from veins? 14.5 What ensures one- way flow of blood through the system? 14.6 Diagram and label the internal structure of the heart, including all valves, chambers, and blood vessels.(Fig. 14.5g) 14.7 Name the blood vessels that connect to each chamber and tell where they are bringing blood from or taking blood to. (Fig. 14- 1, Tbl. 14- 2) 14.8 Name the vessels that supply blood to the heart muscle itself. 14.9 Trace a drop of blood from the left ventricle to the stomach and back to the left ventricle. (Fig. 14- 1) 14.10 Compare the pulmonary circulation with the systemic circulation. (Fig. 14- 1) 14.11 What is a portal system? Name the three portal systems of the body. (Fig. 14- 1) 14.12 How does the cardiovascular system create a region of higher pressure? 14.13 As blood moves away from the heart, what happens to the pressure? Why? (Fig. 14- 2) 14.14 The highest pressure in the blood vessels is found in where, and the lowest pressures are found where? 14.15 What units are used to measure pressure in the cardiovascular system? 14.16 How are myocardial autorhythmic cells anatomically and functionally different from myocardial contractile cells? 14.17 What is a pacemaker potential? (Also see Fig. 12.28, p. 432.) 14.18 Map or diagram the Ca2+- induced Ca2+ release mechanism for contraction in contractile myocardium. Is this more similar to skeletal or smooth muscle? (Fig. 14.9) 14.19 How is Ca2+ removed from the cytoplasm of a cardiac muscle cell? 14.20 How do cardiac muscle cells create graded contractions? 14.21 What causes the unstable membrane potential in myocardial autorhythmic cells? 14.22 Compare the movement of ions during myocardial contractile and myocardial autorhythmic action potentials. (Fig. 14.10 and 14.12) 14.23 How do catecholamines affect the rate of depolarization in pacemaker cells? Describe in terms of ion movement. To which receptor are the catecholamines binding? (Fig. 14.19c,d) 14.24 How does ACh affect the rate of depolarization in pacemaker cells? Describe in terms of ion movement. 14.25 To which receptor does ACh bind? (Fig. 14.19c,e) 14.26 Where do electrical signals in the heart originate? 14.27 What are intercalated disks? (Fig. 14.8) 14.28 What anatomical feature of myocardial cells allows coordinated contraction? 14.29 What cell structures allow electrical signals to spread quickly to adjacent cells? 14.30 Name two functions of the fibrous connective tissue rings that surround openings to major arteries and chambers. ✓ Starting at the sinoatrial (SA) node, draw or map the spread of electrical activity through the heart. Be sure to include all the following terms. (Fig. 14.14) 45 atrial conducting system AV node delay bundle of His left atrium right atrium ventricle atrioventricular (AV) node bundle branches internodal pathway Purkinje fibers septum 14.31 What is the purpose of AV node delay? 14.32 Define a cardiac cycle. 14.33 What is an electrocardiogram (ECG)? (Fig. 14.15) 14.34 What information does an ECG show? 14.35 What is Einthoven’s triangle? (Fig. 14.15b) 14.36 Name the waves of the ECG, tell what electrical event they represent, and with what mechanical event each wave is associated. (Fig. 14.16) 14.37 How does an ECG differ from a single myocardial contractile cell action potential? (Fig. 14.15a,e) 14.38 What is a normal range for heart rate? 14.39 When looking at an ECG, how can you determine the heart rate? 14.40 What electrical event is taking place during the P- R segment on an ECG? 14.41 Explain how you would identify an arrhythmia on an ECG. 14.42 Define systole and diastole. 14.43 Compare and contrast the AV and semilunar valves. 14.44 What are the chordae tendineae and what is their function? How are chordae tendineae related to papillary muscles? 14.45 Is the heart in atrial and ventricular systole at the same time? Explain. 14.46 As the ventricles relax, which valves open? Is blood flowing into the heart? Which chambers? 14.47 In a person at rest, how much of ventricular filling depends on atrial contraction? 14.48 Is there a valve between the atria and venae cavae or pulmonary vein? 14.49 What electrical event precedes ventricular systole? 14.50 As the ventricles contract, why do the AV valves close? 14.51 What creates the heart sounds? 14.52 Explain what is happening during isovolumic ventricular contraction. (Fig. 14.18) 14.53 What happens to pressure within the ventricles during isovolumic ventricular contraction? 14.54 What is happening to the atria during this phase of the cycle? 14.55 What causes the semilunar valves to open, allowing blood to be ejected into the arteries? 14.56 Why do the semilunar valves close? 14.57 When in the cardiac cycle do the AV valves open? 14.58 Define end- diastolic volume (EDV) and end systolic volume (ESV). ✓ Answer the following questions using the pressure- volume loop shown in Fig. 14.17b. At point A, is the atrium relaxed or contracting? Is the ventricle relaxed or contracting? From point A to point B, the ventricular volume is increasing. Why doesn’t ventricular pressure also increase substantially? What happens at A’? What event begins at point B and continues until point D? From point B to point C, why does pressure increase without a change in ventricular volume? What factors are affecting pressure and volume from point C to point D? 46 At point D, why does the aortic valve close? At what point(s) on the graph are both the aortic and mitral valves closed? 14.59 Define stroke volume. (Give units.) 14.60 How do you calculate stroke volume? 14.61 If the end- diastolic volume increases and the end- systolic volume decreases, has the heart pumped more or less blood? 14.62 Define cardiac output (CO). (Give units.) 14.63 What are average values for stroke volume and cardiac output in the 70 kg man at rest? 14.64 Explain the antagonistic control of heart rate by sympathetic and parasympathetic neurons. 14.65 If you were to block all autonomic input to the heart, what would happen to heart rate? 14.66 Name the parasympathetic and sympathetic neurotransmitters and their receptors at the SA node. 14.67 Describe the effects of autonomic modulation on conduction through the AV node. 14.68 What factors affect force of contraction? 14.69 Define contractility. 14.70 State the Frank- Starling law of the heart. 14.71 Define venous return. What cardiac volume does it determine? 14.72 What are three factors that affect venous return? 14.73 Describe the skeletal muscle and respiratory pumps. 14.74 What is an inotropic agent? 14.75 What effect does a positive inotropic agent have on the heart? Name two agents that create a positive inotropic effect. 14.76 How do catecholamines enhance the rate and force of cardiac muscle contraction? 14.77 What kind of receptors are found on the myocardium? (cholinergic/adrenergic?) What is the second messenger system? 14.78 When voltage- gated Ca2+ channels are phosphorylated, their probability of opening is (increased/decreased?) and (more/less?) Ca2+ enters the cell. 14.79 How do cardiac glycosides enhance contractility? Name an example of a cardiac glycoside. What are the therapeutic uses of cardiac glycosides? 14.80 Define and describe afterload. 14.81 What is the ejection fraction? What are normal ejection fraction values for our 70 kg man? 14.82 What is driving pressure? 14.83 What happens to pressure when the heart relaxes or the blood vessels dilate? 14.84 What is a pressure gradient? 14.85 Define resistance. Express this relationship between resistance and flow mathematically: 14.86 Name the three parameters that influence resistance for fluid flowing through a tube. 14.87 Write the equation known as Poiseuille’s law. 14.88 In humans, which these factors in Poiseuille’s law are relatively constant and which play a significant role in determining resistance to blood flow? 14.89 Explain vasoconstriction and vasodilation in terms of diameter and resistance. 14.90 What is the difference between flow (flow rate) and the velocity of flow? (Give units.) 14.91 What factors have the biggest influence on the flow rate? On the velocity of flow? 14.92 Write the equation that expresses the relationship between the flow rate (Q), the velocity of flow (v), and the cross- sectional area (A) of a tube. (Fig. 14.4) 14.93 What is mean arterial pressure (MAP), and what are the two main parameters influencing MAP? 47 The cardiovascular (CV) system is a system of pumps and pipes, with fluid flowing through them. Therefore, the CV system largely operates according to the physical principles of fluid flow. ✔ What are the “pumps?” ___________________________________________________________ ✔ Are these pumps in series or parallel? ________________________________________________ ✔ What are the “pipes”? _____________________________________________________________ ✔ What portion of the “pipes” provides variable resistance? _________________________________ ✔ Fluid only flows if there is a ________________________________________________________ ✔The opposition to flow is known as ___________________________________________________ ✔ Write the equation that expresses the relationship between flow and the last 2 factors that you wrote in the blanks above. ✔ Write the equation for resistance to fluid flow through a cylinder. ✔ List the parameters of this equation that are normally variable in humans: ✔ Compare the action potentials of a myocardial contractile cell to those of a neuron. Neuron Myocardial contractile cell Resting membrane potential (mV) Stimulus to begin action potential Rising phase (ions, direction) Falling phase (ions, direction) Hyperpolarization Duration of action potential 48 ✔ Now describe the action potentials of a myocardial autorhythmic cell: Myocardial autorhythmic cell Resting membrane potential (mV) Stimulus to begin action potential Rising phase (ions, direction) Falling phase (ions, direction) Hyperpolarization Duration of action potential ✔ What is the functional importance of: a) nonconducting tissue between the atria and ventricles? b) AV node delay? ✔ Adapting the model shown in Figure 14.9 (p. 478), diagram the modulation of cardiac contraction by catecholamines. Use Fig. 14.17a to answer these questions: ✔ What happens to ventricular volume during isovolumic ventricular contraction? ________________________________________________________________________________ ✔ What happens to ventricular pressure during isovolumic ventricular contraction? _________________________________________________________________________________ ✔ In what position are the AV and semilunar valves during isovolumic ventricular contraction? AV are ________________________________. Semilunar are _______________________________. ✔ Autorhythmic cells have what type(s) of neurotransmitter receptors? 49 CHAPTER 15 READING QUESTIONS Chapter 15 15.1 Name the four tissue layers found in blood vessel walls, starting with the layer closest to the lumen. (Fig. 15- 2) 15.2 Describe the key physical differences of the aorta, major arteries, arterioles, capillaries, venules, and veins. (Fig. 15- 2) 15.3 How do the capillaries of the blood- brain barrier differ from those in the rest of the systemic circulation? 15.4 How much of the blood in the circulatory system is found in the veins? 15.5 What property of artery walls plays a key role in the ability of arteries to sustain the driving pressure created by the heart? (Fig. 15.5) 15.6 Why does blood pressure decrease as blood flows through the circulatory system? 15.7 Define systolic and diastolic pressure and give an “average” value for these arterial pressures. 15.8 What is pulse pressure and how do you calculate it? 15.9 How do you calculate mean arterial pressure (MAP)? 15.10 What kinds of problems might result when blood pressure is too low? Too high? 15.11 Explain how a sphygmomanometer measures arterial pressure of the radial artery. (Fig. 15- 7) 15.12 What makes Korotkoff sounds? 15.13 What is the medical term for high blood pressure? You are considered to have high blood pressure if your readings are chronically above what value? Your blood pressure is borderline- high if it is chronically above what value? 15.14 What two main factors determine mean arterial pressure (MAP)? (Fig. 15.8a) 15.15 What happens to MAP if peripheral resistance increases? 15.16 Which two body systems are responsible for homeostatic regulation of blood pressure? (Fig. 15- 9) 15.17 Name two ways the cardiovascular system tries to compensate for a decrease in blood volume. 15.18 If arterial pressure falls, venous constriction mediated through the (sympathetic/parasympathetic?) division will have what effect on blood distribution and blood pressure? 15.19 Which vessels are the main site of variable resistance in the systemic circulation? 15.20 Write the mathematical expression for the relationship between radius and resistance. 15.21 List the chemicals that mediate arteriolar resistance by producing vasoconstriction or vasodilation. 15.22 What is myogenic autoregulation? Explain the mechanism by which it occurs. 15.33 Tonic norepinephrine + ____ receptors = myogenic tone Norepinephrine or epinephrine + ____ receptors = reinforcement of vasoconstriction α receptors are most sensitive to which neurotransmitter? (Also see Tbl. 11- 2.) epinephrine + ____ receptors results in vasodilation of selected arterioles 15.34 Why don’t all tissues get equal blood flow at all times? 15.35 At rest, which four organ systems receive most blood flow? (Fig. 15.12) 15.36 Are arterioles arranged in series or parallel? 15.37 At any given moment, the total blood flow through all arterioles = _________. 15.38 When resistance of an arteriole increases, blood flow through it (increases/decreases?). 15.39 When blood flow decreases through one set of arterioles, where does that blood go? 50 15.40 In what part of the brain is the neural control center for blood pressure homeostasis found? 15.41 Where are the two main receptors for blood pressure located? What types of sensory receptors are they? 15.42 What is significant about their locations? Are these receptors tonic or phasic? (Fig. 15.14a) 15.43 Match the components of the baroreceptor reflex to the standard steps of a reflex (sensor, afferent path, etc.) (Fig. 15.14a) 15.44 An increase in sympathetic activity will have what effect on heart rate, force of contraction, arteriolar diameter, and MAP? 15.45 What is orthostatic hypotension? Why does blood pressure initially fall when standing up after lying flat? 15.46 Map the reflex response to increased mean arterial pressure. (Fig. 15.14b) 15.47 Explain the relationship between total cross- sectional area and velocity of flow in the circulatory system. Specifically, how does the total cross- sectional area of capillaries compare to that of larger- diameter blood- vessels? (Fig. 15.17) 15.48 Capillary pores are too small to allow proteins to pass through them. How then do protein hormones and other essential proteins move out of the blood and into the interstitial fluid? (Fig. 15.16) 15.49 Define bulk flow. 15.50 What creates the osmotic pressure gradient between the blood and the interstitial fluid? 15.51 What is colloid osmotic pressure (π)? 15.52 What forces create filtration and absorption in capillaries? What determines net flow across capillary walls? (Fig. 15.18) 15.53 Name the three systems with which the lymphatics interact and explain the role of the lymphatics in each system. 15.54 Compare the anatomy of the lymphatic system to that of the circulatory system. 15.55 Where does lymph rejoin the blood? 15.56 Name the factors that influence fluid flow through the lymphatics. (Does the lymph system have a pump like the heart?) 15.57 What is edema? ✔ A person has a blood pressure of 85/60 and a heart rate of 70 bpm. What is this person’s mean arterial pressure? pulse pressure? Can you calculate the cardiac output? ✔ Draw and label a graph showing the effect of cardiac output on arterial blood pressure. Make sure your axes are labeled correctly! 51 Mean arterial pressure is a function of: 1. cardiac output 2. peripheral resistance 3. distribution of blood between arteries and veins 4. blood volume Factor 1 can be altered by changing _____________________________________________________ Factor 2 can be altered by changing ______________________________________________________ Factor 3 can be altered by changing ______________________________________________________ Factor 4 can be altered by changing_______________________________________________________ ✔ Which of these four factors is/are subject to homeostatic regulation? Go back and put the neurotransmitter or hormone, its receptor, and the division of the nervous center doing the control next to the appropriate changes. FACTORS AFFECTING BLOOD FLOW: Poiseuille's Law: Flow = π ·ȡ Δ P ·ȡ r4/8 η L ✔ Rewrite the equation eliminating those variables that normally do not significantly affect blood flow in the body. Flow ∝ _______________________________________ ΔP - The pressure gradient is the difference between the pressure at any two points in the system. ✔ For flow through the systemic circulation, we would look at the pressure gradient between what two anatomical locations? ✔ P1, the highest pressure would be found in the ___________________________ . ✔ P2, the lowest pressure would be found in the ___________________________ . ✔ Using Fig. 15.6 (p. 514), what value would you use for P1? ____________. In words, this value is called the _____________________________. What value would you use for P2? ___________ Substitute those values into the equation ΔP = P1 - P2 Now substitute the alternate expression for ΔP into the following equation: Flow = ΔP / R Flow = 52 ✔ What one factor influences R the most?_______________________________________ ✔ Relate this factor to resistance mathematically: ✔ Substitute the alternate expression for resistance into the flow equation: Flow = ✔ Distinguish between: a) pressure and ΔP b) flow rate and velocity of flow ✔ List the four primary determinants of mean arterial pressure. (1) __________This determinant can be altered by changing _______________ or __________________, (2) __________________________________ (3) __________________________________ (4) __________________________________ 53 CARDIOVASCULAR PROBLEMS (CHAPTERS 14, 15) 1. Below are 2 pipes with fixed resistance. Compare the flow rates between tubes A and B below. (assume fluid same viscosity) Flow A Flow B P1 = 125 mm Hg r = 2 P2 = 75 mm Hg L = 16 Tube A P1 = 180 mm Hg P2 = 100 mm Hg r = 1 L=2 Tube B 2. If blood pressure remains constant, what change in mean arteriolar resistance must occur in order to double blood flow? (one answer) a. double b. decrease by half c. increase by a factor of 16 d. decrease by r4 3. If the total cross- sectional area of the capillaries is 5000x greater than that of the aorta, then the velocity of flow in the capillaries must be the velocity in the aorta. a. 1/5000th b. 5000x greater c. 1/200th d. 200x greater 4. Given this statement: Flow rate is lowest in the capillaries because flow rate must be low for exchange to occur? a. Is this statement true? If not, correct it. b. Is it teleological or mechanistic? Re- word it to be the opposite. 5. Recreate William Harvey’s work. If blood weighs 1 g per mL, and the heart beats at a rate of 70 beats per minute and pumps 65 mL per beat, what is the weight of the blood pumped in one hour? How does this compare to the weight of the “average” 154 lb. male? 54 6. A person has a blood pressure of 85/60 and a heart rate of 70 bpm. What is this person’s mean arterial pressure? pulse pressure? Can you calculate the cardiac output? 7. If the stroke volume of the right ventricle is 70 mL per beat and the stroke volume of the failing left ventricle is 69.99 mL per beat, what will happen to the relative distribution of blood between the systemic and pulmonary circulation after 1 hour if the heart rate is 70 beats/min? 8. Circle all that pertain to PACEMAKER cells, but NOT to contractile cells. Innervated by the vagus nerve have channels that open at – 55 mV Repolarization represented by an ECG wave slow depolarization to threshold No high resting permeability to any one ion symp increases Ca2+ uptake by SR Regulate rate of heart beat Ca2+ action potentials 9. Which statements about the ECG below are true? a) If you took this person’s pulse, the heart beat would be irregular. b) If you took this person’s pulse, the heat beat would have a rate within normal limits. c) Conduction through the AV node appears to be normal. d) Conduction of action potentials through the ventricles appears to be normal. 10 seconds 10. Both traces below are recorded from individuals with the same ectopic pacemaker. On BOTH ECG traces, select a complex and label the waves. Trace 1 Trace 2 The normally sets the pace for the heart because: (circle all correct) a. Of its position in the heart c. It is innervated by sympathetic neurons b. It depolarizes at the fastest rate d. It conducts the fastest Which pacemaker is ectopic in the two traces above? Briefly explain your answer. 11. Why is the small wave inverted in trace 2 (see above)? 55 12. Which comes first? Circle the one that comes first or causes the other event. If the 2 are synonymous, circle both. AV valve closure PR segment T wave ventricular relaxation Signal through intermodal pathways signal through atrial contractile cells Heart sound 2 ST segment (following blood movement from the vena cavae:) Blood movement through pulmonary arteries through pulmonary vein 13. Questions 13- Myocardial Infarction case study: While driving home from work, Leonard suffered a myocardial infarction (heart attack) causing him to lose consciousness and drive off the road. A myocardial infarction is caused by reduced blood flow to the heart through the coronary arteries. Reduction of blood flow occurs when coronary arteries are narrowed, such as occurs with atherosclerotic plaques. 23. If the diameter of Leonard’s left coronary artery was only 1/3 of normal, by how much was blood flow to his heart reduced? 14. You’ll be glad to know that Leonard received prompt treatment and not only survived but recovered a high percentage of function. However, once a (non-fatal) heart attack has occurred, conduction through the heart changes. a. First, hypoxia causes uncoupling of connexons, proteins that form --structures that link the heart cells into a syncytium. 15. Hypoxia has been shown to cause an upregulation of sympathetic activity, resulting in “↑ plateau current.” This increase in plateau current can lead to “Ca2+ store overload” and can result in “afterpotentials” which then cause arrhythmias. a. Which of the following always is an arrhythmia or results in arrhythmia? V-fib partial heart block complete heart block A-fib b. Which cell type is under consideration in question 25? c. Compare and contrast pacemaker and contractile cells and their action potentials. Note: there are a few more cardiovascular questions at the end of the respiratory questions. See “Integrated Cardiovascular and Respiratory Questions” 56 Class exercise: Pressure- volume curve and Wiggers diagram Show on the graph where the following occur in the left ventricle: 1—ventricular relaxation begins 3—ejection of blood occurs 2—diastolic pressure in the aorta 4—mitral valve opens 5- - - end diastolic volume A Ventricular pressure B E D C Ventricular volume In the diagram below: Atrial systole begins just before letter _____. Ventricular depolarization just before point _____ Isovolumic relaxation occurs between _____ and _____ Stroke volume is ejected between _____ and _____ The mitral valve opens at _____ The aortic valve is open between _____ and _____ Ventricular blood volume is at its lowest level at ___ 57 Discussion Exercise – Cardiovascular – ECG 1. Draw a flowchart illustrating the normal impulse conduction through the heart. How is the depolarization conveyed from cell to cell? 2. An electrocardiogram is a sum of all the electrical activity of the heart, recorded from the surface of the body. For the normal ECG below: 3 sec a. Label the waves and segments. b. Calculate the heart rate. c. Which wave, segment or interval would you analyze to determine: AV node delay Atrial rhythm Conduction through ventricular muscle Refractory period of contractile AP d. In which part of the ECG does the ventricular Na+ influx occur? 3 a. .How would the trace in #2 change under sympathetic influence on pacemaker cells? b. Describe the cellular mechanisms that lead to those changes 58 4. Can heart rate be accurately determined in the recording below? In which pacemaker does the condition originate? 5a.The following strips illustrate a fairly common pathology. b. What pathology is present in both traces? What is the condition called? What is the difference between the recording in a versus b? 6. a. b. Identify the above two traces as V- fib (ventricular fibrillation) or A- fib (atrial fibrillation). What characteristic distinguishes A- fib from V- fib? Why is V- fib more serious a pathology than A- fib? 59 RESPIRATORY PHYSIOLOGY NOTE: Unless otherwise specified, the terms “arterial blood” and “venous blood” refer to blood in the systemic circulation. The modifier “pulmonary” is used for blood in the pulmonary circuit. READING QUESTIONS FOR CHAPTER 17 17.1 List four primary functions of the respiratory system. 17.2 What is lost from the body through the respiratory system besides carbon dioxide? 17.3 Distinguish between cellular respiration and external respiration. 17.4 List the four integrated processes of external respiration (three exchanges and one transport). (Fig. 17- 1) 17.5 Distinguish between inspiration and expiration. 17.6 Name the structures of the upper and lower respiratory system, following an oxygen molecule from air to the exchange surface of the lungs. Briefly describe the anatomy of each section. (Fig. 17.2) 17.7 What bones and muscles form the thoracic cage? The floor? (Fig. 17.2b) 17.8 Name the two additional sets of muscles associated with the thoracic cage. 17.9 Name the three sacs enclosed within the thorax. What is in each sac? (Fig. 17.2c) 17.10 What thoracic structures are not contained within these three sacs? 17.11 What is the relationship between the lungs, the pleura, and the pleural fluid? (Fig. 17- 3) 17.12 What purposes does pleural fluid serve? 17.13 Which air passages of the respiratory system are collapsible? 17.14 List 3 functions of the upper airways and bronchi in addition to simply being passageways. 17.15 Describe and give the functions of the two types of epithelial cells in alveoli. What kind of epithelia are these two cell types? (Fig. 17- 2g) 17.16 Describe the association of the alveoli and the circulatory system. (Fig. 17- 2h) 17.17 Trace a drop of blood through the pulmonary circulation from the (left/right?) ventricle to the (left/right?) atrium. 17.18 Compare pulmonary blood flow, blood pressure, and capillary filtration to that of the systemic circuit. 17.19 Distinguish between: – intrapulmonary, alveolar, and intrapleural pressure (Fig. 17.9, 17.10) – atmospheric pressure and partial pressure – lung volumes and lung capacities (Fig. 17.7) – inspiration and expiration – active and passive expiration – total pulmonary ventilation and alveolar ventilation (include equations) – restrictive and obstructive lung disease – hyperventilation and hyperpnea (Tbl. 17.2) – anatomic dead space and physiological dead space 17.20 How does increasing water vapor pressure in a mixture of gases affect the concentration of those gases if nothing else changes? (Fig 17.6c) 17.21 In which air passage(s) of the respiratory system is resistance to flow (normally) greatest? 17.22 At what point in a respiratory cycle is intrapleural pressure greatest? least? equal to atmospheric pressure? (Fig. 17.9) 17.23 What is the role of surfactant in the alveoli? What happens if it is lacking? (Fig. 17.11) 60 17.24 What local factors influence resistance in the bronchioles? in the pulmonary arterioles? (Fig. 17.14) ✔ What is the partial pressure of oxygen in dry air at the top of Mt. Everest, where the atmospheric pressure is measured as 253 torr? ✔ Compare factors that affect air flow in the respiratory system to factors that affect blood flow through arterioles. ✔ Explain the adaptive significance of the fact that low tissue oxygen concentrations in the lungs constrict pulmonary arterioles rather than dilate them. CHAPTER 16 READING QUESTIONS (pp. 545- 557) 16.1 What is erythropoietin (EPO) and where is it made? What is the stimulus for EPO synthesis and release? 16.2 Define hematocrit. What is the abbreviation for hematocrit? (Fig. 16- 3) 16.3 Describe the structure and contents of the mature RBC. 16.4 What is the primary source of ATP for mature RBCs? 16.5 How is the lack of a nucleus related to the limited life span of the RBC? 16.6 Why does an erythrocyte need to be flexible? 16.7 Describe or draw the structure of hemoglobin (Hb). 16.8 Why must we have adequate iron in the diet in order to make hemoglobin? 16.9 What is the average life span of an RBC? 16.10 How are old RBCs destroyed and what happens to the RBC components? 16.11 What is the relationship between heme, bilirubin, and bile? 16.12 What is polycythemia (two forms)? CHAPTER 18 READING QUESTIONS ☞༅ Review the law of mass action, p. 102. 18.1 By what mechanism do gases move between the alveoli and the plasma? 18.2 List the four rules for diffusion of gases. (See Tbl. 5.6.) 18.3 Why do respiratory physiologists commonly use partial pressures to express gas concentrations in solution? 18.4 When a gas is placed in contact with a liquid, what three factors determine how much gas will dissolve in the liquid? 18.5 The more soluble a gas is in a particular liquid, the (higher/lower?) the partial pressure required to force the gas into solution. (Fig. 18.4) 18.6 Which is more soluble in body fluids: oxygen or carbon dioxide? 18.7 Fill in the “normal” values for the following partial pressures in a person at sea level: (Fig 18.2, Tbl 18.2) PO2: Alveoli = ______ Arterial blood = ______ Resting cells = _______Venous blood = _______ PCO2: Alveoli = ______ Arterial blood = ______ Resting cells = _______Venous blood = _______ 18.8 Define hypoxia and hypercapnia. 61 18.9 List 3 pathological changes in the alveolar- blood exchange surface that result in low arterial content. (Fig. 18.3c) 18.10 List the two main reasons alveolar PO2 may be lower than normal. 18.11 What two cell layers must gases cross to go from the alveoli to the plasma? (Fig. 18.3b) 18.12 How much of the alveolar epithelium must be incapacitated before arterial PO2 drops? 18.13 What is pulmonary edema and how does it alter gas exchange? 18.14 List two ways that gases are transported in the blood. 18.15 _______% of oxygen in a given volume of blood will be carried bound to hemoglobin. (Fig. 18.5) 18.16 The amount of O2 bound to Hb depends primarily on what two factors? (Fig. 18- 10) 18.17 What determines the number of Hb binding sites for oxygen? 18.18 What is the “corpuscle” in the term mean corpuscular Hb? 18.19 Describe the differences between adult and fetal hemoglobin. 18.20 Explain how oxygen- hemoglobin binding obeys the law of mass action. 18.21 As dissolved O2 diffuses into RBCs, what happens to the PO2 of the surrounding plasma? 18.22 In the oxyhemoglobin dissociation curve (Fig. 18- 9a), the (PO2 / percent saturation of Hb) determines the (PO2 / percent saturation of Hb). 18.23 Below PO2 of 60 mm Hg, where the curve is steeper, small changes in PO2 cause relatively (small/large?) releases of O2 from hemoglobin. 18.24 An increase in pH (increases/decreases?) hemoglobin’s affinity for oxygen. (Fig. 18- 9c) 18.25 An increase in temperature (increases/decreases?) hemoglobin’s affinity for oxygen. (Fig. 18- 9d) 18.26 An increase in PCO2 (increases/decreases?) hemoglobin’s affinity for oxygen. (Fig. 18- 9e) 18.27 The metabolite 2,3- DPG (increases/decreases?) hemoglobin’s affinity for oxygen. What triggers an increase in 2,3- DPG production? (Fig. 18.9f) 18.28 Fetal Hb has a/an (increased/decreased?) affinity for oxygen. (Fig. 18.9b) 18.29 A left shift in the curve indicates (increased/decreased?) binding affinity. 18.30 A right shift in the curve indicates (increased/decreased?) binding affinity. 18.31 Why is it important that CO2 be removed from the body? 18.32 List the three ways CO2 is transported in the blood. (Fig. 18- 11) 18.33 Write the equation, including the enzyme, in which CO2 is converted into bicarbonate ion (HCO3– ) and H+. 18.34 What two purposes does the conversion of CO2 to HCO3– serve? 18.35 What is the chloride shift? 18.36 What is a buffer? 18.37 Compare the rhythmicity and control of breathing to that of the heartbeat. 18.38 Compare the types of efferent neurons leaving the respiratory control center and the cardiovascular control center. (Fig. 18- 13) 18.39 What role do each of the following play in the control of breathing? a. medulla oblongata: b. pons: c. cerebrum: 18.40 Describe neural control of quiet respiration. (Fig. 18- 14) 18.41 List the location and the chemical factor(s) monitored by each group of respiratory chemoreceptors. 18.42 Explain the strategic significance of the location of the peripheral chemoreceptors. (Fig. 18- 13) 62 18.43 Using the oxyhemoglobin dissociation curve in Fig. 18- 9a, explain the adaptive significance of the fact that the peripheral chemoreceptors do not respond to decreases in PO2 until the PO2 drops below 60 mm Hg. 18.44 An increase in PCO2 will trigger a/an (decrease/increase?) in ventilation. (Fig. 18- 17) 18.45 If PCO2 is chronically elevated (chronic hypercapnia) and hypoxia, is CO2 the primary chemical drive for ventilation? Explain. 18.46 Write the reflex response to an inhaled irritant. sensor afferent pathway integrating center efferent pathway (include chemicals and receptors) effector tissue response systemic response 18.47 Give two examples of how higher brain centers can alter ventilation. ✔ Suppose the partial pressure of atmospheric O2 and CO2 on a different planet were 40 mm Hg each. In an open glass of water, would more O2 be dissolved or CO2? Or would concentrations be equal? ✔ Suppose there were only one hemoglobin molecule, to which were bound 3 oxygens. What is the % saturation? What if there were a billion Hb molecules, each with 3 oxygens bound? ✔ At equilibrium, the (concentration / partial pressure / both?) of a gas will be equal in the air and gas phases. ✔ TRUE/FALSE? Defend your answer. If a liquid is exposed to a PCO2 of 100 mm Hg and a PO2 of 100 mm Hg, equal amounts of oxygen and carbon dioxide will dissolve in the liquid. (Fig. 18.4) ✔ If the alveolar PO2 is 98 mm Hg, what will the arterial PO2 leaving the lungs be? Explain. ✔ What would happen to venous transport of CO2 if H+ and HCO3– were not removed from RBC cytoplasm? Explain. ✔ Answer the graph questions for Fig. 18- 9. ✔ Create a map of carbon dioxide transport, using the following terms. You may add additional terms. CO2 carbaminohemoglobin carbonic anhydrase carbonic acid Pco2 dissolved CO2 hemoglobin Cl− pH chloride shift H+ buffer bicarbonate plasma - HCO3 red blood cell 63 RESPIRATION PROLEMS (CHAPTERS 17 & 18) 1. Inhaled air becomes completely humidified as it passes through the upper respiratory tract. The partial pressure of water vapor in inspired air is 47 mm Hg by the time inhaled air enters the alveoli. If atmospheric pressure is 700 mm Hg and oxygen is 21% of the atmosphere at 0% humidity, estimate the arterial PO2 in a person breathing this air. 2. Maximum Voluntary Ventilation (MVV) is a pulmonary function test that similar to recording total pulmonary ventilation, except that the subject breathes as rapidly and forcefully as possible. This maximal volume breathed is equal to his vital capacity (VC). a. Given this information, write the formula for MVV: b. A subject named Hank performs the MVV test. If he weighs 200 lbs, and his VC = 5.2 L, and he breathes 25 breaths/min, calculate his alveolar ventilation. c. Given the info above and that his heart rate is 100 bpm and his SV is 250 mL/beat, calculate his ventilation/perfusion . d. Use his V/P ratio to explain why Hank cannot sustain this maximal voluntary ventilation rate for very long. 3. Compare the following pairs of items, using <, >, or =. In all situations, assume all other factors to be equal and the conditions given are the only under consideration. Airway resistance in presence of high ACh Airway resistance with low ACh TPP in pneumothorax TPP at end of normal expiration Bronchiolar diameter if alveolar PCO2 = 40 Bronchiolar diameter if PCO2 = 45 mm Hg Total lung capacity forced vital capacity Alveolar PCO2 atmospheric PCO2 Re: the normal pulmonary pressures graph TPP at end of expiration TPP at end of inspiration Intra- alveolar pressure intrapleural pressure Intrapleural pressure at end of inspiration intrapleural pressure at end of expiration 64 4. Presence of irritants in the airways triggers a cough reflex to expel the irritants. This reflex has several phases. Phase 1 results in bronchoconstriction, preventing irritant from descending into lungs. In phase 2, the irritant is expelled by a strong expiratory effort. For each phase, list the following. Phase 1 Phase 2 Neurotransmitter Receptor subtype Effector(s) 5. Patients with advanced emphysema often must use portable “oxygen tanks.” These tanks actually have a mix of gases with a high oxygen content. If the tank contains the following mix at the given pressures, what is the percent of oxygen? Answer: % Nitrogen 350 mm Hg Oxygen 400 mm Hg Carbon dioxide 45 mm Hg Water vapor 5 mm Hg 6. Fetal hemoglobin has a higher affinity for O2 than does maternal hemoglobin. Given the following information, calculate maximum O2 carrying capacity per gram of fetal Hb. Maternal Fetal HbO2/dL blood 19.6 mL/dL 18.7 mL/dL % saturation 97.5% 99% Max. O2 1.34 mL O2/g Hb ???? capacity Amount Hb 15 g/dL 13.5 g/dL 65 Integrated Cardiovascular and Respiratory Questions 1. Of the following pairs on each line below, write 1 by the event that happens first. If the events happen at the same time, write 1 by both. _____Conduction through AV node _____ conduction through Purkinje fibers _____conduction through right bundle branch _____ conduction through left bundle branch _____QRS wave _____ right ventricular systole _____decrease in transpulmonary pressure _____ movement of air out of the lungs 2. Fill in the compare/contrast chart below for the CV and respiratory systems: Cardiovascular Respiratory Site of variable resistance Location of the pacemaker Neural control of resistance comes from the _____________division Muscle type of the system’s “pump” Location of CNS control center 3. Autonomic control mechanisms Receptor Tissue Response bronchiolar smooth muscle dilation ACh SA node ventricles increased force arteriolar smooth muscle dilation NT or NH arteriolar smooth muscle constriction 66 4.Comparisons. Compare the 2 items in each line and circle the one of each pair that is greater. If the 2 are equivalent, circle both. Heart rate when R- R interval is 0.75 sec heart rate when R- R interval = 0.5 sec Transpulmonary pressure at end of inspiration TPP at end of expiration Total pulmonary ventilation with 12 breaths/min alveolar ventilation with 12 breaths/min MAP, if systolic = 140, diastolic = 90 Normal intrapleural pressure intrapleural pressure in pneumothorax Bronchiolar diameter with ↑ ACh bronchiolar diameter with ↑ CO2 Use of internal intercostals due to fibrosis use of internal intercostals due to emphysema % saturation in anemia due to blood loss % saturation in CO poisoning Conduction velocity through AV node conduction velocity through Purkinje fibers pulse pressure (systolic = 140, diastolic = 90) 5. Compare the cardiovascular & respiratory systems by filling in the blanks in the table. As an example, the first comparison is filled in. Respiratory Cardiovascular bronchioles arterioles Total pulmonary ventilation Effect of Epi on β2: Effect of Epi on β2: Role of elastin—to generate: role of elastin—to generate: _________________ Pressure ___________________Pressure End systolic volume Velocity of flow is lowest in the: Velocity of flow is lowest in the: Athe 6. A student in an undergraduate physiology lab volunteered to be the subject for ECG experiments. One experiment examined the effect of apnea on heart rate. She held her breath for 45 seconds as her heart electrical activity was recorded from lead II. Upon analysis, she was surprised to learn that her R- R interval increased from 0.80 sec to 1.2 sec. This change in heart rate is called: (circle) bradycardia tachycardia This effect is similar to the effect of on the heart (circle all correct): a. Acetylcholine c. Norepinephrine b. Epinephrine d. Nitric oxide 67 RENAL PHYSIOLOGY CHAPTER 19 READING QUESTIONS 19.1 State the law of mass balance. 19.2 List the six functions of the kidneys: 19.3 Starting at the renal pelvis, trace a drop of urine to the external environment, naming all structures it passes. (Fig. 19- 1a) 19.4 Describe the vascular supply to the kidneys. 19.5 What is the function of the urinary bladder? 19.6 What is a nephron? Trace a drop of fluid from afferent arteriole through the tubule of the nephron, ending in the renal pelvis, naming all structures it passes. (Figs. 19- 1c, j, 19- 2) 19.7 Describe the portal system of the kidney. 19.8 What is the renal corpuscle? What happens here? 19.9 Describe the juxtaglomerular apparatus. (Fig. 19- 7) 19.10 How much plasma on average enters the nephrons per day? 19.11 How much urine on average leaves the body per day as urine? What happens to the fluid that doesn’t leave in the urine? 19.12 Name the three processes of the kidney and describe them. Write the equation that relates excretion to these three processes. In which of these processes is fluid entering the external environment? Which process(es) is bulk flow? Which process(es) uses transporting epithelia? 19.13 Describe the composition of the filtrate that enters the lumen of the nephron. 19.14 Describe the three filtration barriers a water molecule must cross as it travels from the blood into the lumen of Bowman’s capsule. 19.15 What are mesangial cells and what is their function? (Fig. 19- 5) 19.16 What two factors influence GFR the most? 19.17 An average value for GFR is __________ L/day or ______________ mL/min. 19.18 The total body plasma volume is _________ L, which means that the kidneys filter the plasma________ times each day. 19.19 What is the relationship between blood pressure and GFR? (Fig. 19- 6b) 19.20 What is meant by autoregulation of GFR? By what two mechanisms does your body accomplish autoregulation of GFR? 19.21 Describe the myogenic response of the afferent arteriolar smooth muscle to increased blood pressure. 19.22 Why is vasodilation not as effective as vasoconstriction in controlling GFR? 19.23 Why is decreased GFR when blood pressures fall below normal an adaptive response? 19.24 Describe tubuloglomerular feedback as a result of increased blood pressure. (Fig. 19- 7c) 19.25 In neural control of GFR, (sympathetic/parasympathetic?) neurons release (ACh/norepi?) onto (α, β1, β2?) receptors, causing (vasodilation/vasoconstriction?) of renal arterioles. 19.26 Vasoconstriction of the afferent arteriole will (increase/decrease?) its resistance, which will (increase/decrease?) hydrostatic pressure in the glomerular capillaries, and will (increase/decrease?) GFR. 19.27 Vasoconstriction of the efferent arteriole will (increase/decrease) its resistance, which will (increase/decrease?) hydrostatic pressure in the glomerular capillaries, and will (increase/decrease?) GFR. 68 19.28 Bulk reabsorption in the nephron takes place in the ______________. Which ion plays a key role in bulk reabsorption? 19.29 To reabsorb molecules against their concentration gradient, the transporting epithelia of the nephron must use what process? 19.30 Filtrate entering proximal tubule has Na+ similar to that of ______________ and (higher/lower?) than the Na+ inside cells. 19.31 Diagram the transepithelial movement of Na+ across proximal tubule cells. Include transporter proteins involved. 19.32 List some molecules that are transported using Na+- linked secondary active transport. 19.33 For each of the following substances, tell how it crosses the apical and basolateral membranes of the proximal tubule cell and what form of transport it uses at each membrane (primary active, secondary active, facilitated diffusion, simple diffusion): Na+, glucose, water, urea, proteins (Fig. 19- 11, 19- 13). Be able to diagram these processes. 19.34 List the three properties of mediated transport seen in all protein- substrate interactions. (See pp. 39- 45.) 19.35 For a particular substance, the plasma concentration at which that substance first appears in the urine is known as the _________________________. (Fig. 19- 10) 19.36 Filtration (does / doesn’t?) exhibit saturation. (Fig. 19- 10a) 19.37 What happens when the concentration of a substance in the plasma exceeds its renal threshold? (Figs. 19- 10c, d) 19.38 How does fluid reabsorbed from the lumen of the nephron tubule system get reabsorbed into the peritubular capillaries? 19.39 What is the point of secreting a substance in addition to filtering it? 19.40 When probenecid is given at the same time as penicillin, what happens to the excretion rate of penicillin? Why? 19.41 Does looking at the composition of urine tell us if a substance has been filtered? ____________ 19.42 reabsorbed? ______________ secreted? ______________ excreted? __________________ 19.43 Define clearance, give its units, and write the mathematical equation. (Fig. 19- 13) 19.44 When can you use a clearance rate to estimate GFR? 19.45 If you haven’t done so yet, work the example in concept check #12 on p. 649. Clearance can be tricky at first, so the more practice, the better! 19.46 How can you use clearance values to determine renal handling of a substance? 19.47 Distinguish between: a. excretion and secretion b. renal cortex and medulla c. glomerular filtration and systemic capillary filtration. (See pp. 529- 531.) d. filtration fraction (Fig. 19- 4) and GFR e. transepithelial transport and the paracellular pathway f. renal handling of a substance and its clearance 19.48 What is the function of the urinary bladder? 19.49 List the bladder muscles, their muscle type (skeletal or smooth), and their neural control. 69 Equations to remember! ☛ Excretion = Filtration − Reabsorption + Secretion (E = F −R + S) ☛ Plasma [χ] × GFR = amount χ filtered/ unit time or filtration rate of χ ☛ urine conc. (Ux) × urine flow (V) = [χ]/min or the rate at which χ is excreted ☛ clearance = urine conc. (Ux) x urine flow (V) = excretion rate of x plasma conc (Px) plasma conc of x What is the relationship between clearance and GFR? GFR = inulin excretion rate = inulin clearance plasma [inulin] ★ For any filterable substance, by comparing its clearance to GFR, you can tell how the kidney is handling the substance. ✔ Explain how the principle of mass balance applies to secretion, excretion, reabsorption, and filtration. ✔ Give two teleological reasons why our kidneys filter, then reabsorb such large volumes of fluid each day. ✔ What does it tell you if the clearance of a substance is less than the GFR? _________________ equal to GFR? ____________________________ more than GFR? ________________________ ✔ An average value for GFR is __________ L/day or ______________ mL/min. ✔ If urine concentration of inulin is 29 mg/mL, urine flow is 1.1 mL/min, and plasma inulin is 0.25 mg/mL, what is the GFR? CHAPTER 20 READING QUESTIONS - Fluid and electrolyte balance 20.1 What role do the kidneys and lungs play in maintaining mass balance? 20.2 How does behavior factor into the maintenance of fluid/electrolyte homeostasis? 20.3 In a 70- kg man, how much water is in his entire body? ICF? ECF? plasma? (Fig. 5.1b, Table 5.1) 20.4 List or diagram the normal routes of water input and water loss for the body. Which are the most significant?. 20.5 What is insensible water loss? 20.6 Give some examples of pathological water loss. 20.7 When water is lost from the body, how can it be restored? 70 20.8 By what process do the kidneys eliminate excess water? By what process do the kidneys conserve water? 20.9 What are the primary functions of the loop of Henle? 20.10 How does the collecting duct alter its permeability to water and determine final urine concentration? (Fig. 20- 5) 20.11 Diagram the cellular mechanism of action of vasopressin. 20.12 Create a reflex map for vasopressin regulation of water balance. What stimuli control vasopressin secretion? 20.13 When osmolarity increases above ________ mOsM, vasopressin release is (stimulated/inhibited?), leading to (increased/decreased?) renal water reabsorption. 20.14 What is the key to the kidney’s ability to produce concentrated urine? 20.15 The descending limb of the loop is permeable to (water/solutes?) and impermeable to (water/solutes?). 20.16 The ascending limb is permeable to (water/solutes?) and impermeable to (water/solutes?). As a result of the countercurrent system, fluid leaving the loop is (hypo- / iso- / hyper- ?) osmotic to the blood. 20.17 What is normal body osmolarity? 20.18 The addition of NaCl to the body raises osmolarity. This stimulus triggers what two responses? 20.19 Regulated sodium excretion is a function of the kidneys. What are other ways sodium leaves the body? 20.20 If aldosterone behaves like a typical steroid hormone, then describe how it is made; stored, secreted, and transported to its target. Describe its cellular mechanism of action. (See Ch. 7 for these details) 20.21 What are the target cells for aldosterone, and where are they located? 20.22 Describe or diagram the cellular mechanism of action of aldosterone. 20.23 The stimuli that begin the RAAS pathway are all related directly or indirectly to what? 20.24 List the effects of ANGII beyond stimulating aldosterone secretion. (Fig. 20- 10) 20.25 What is ANP? Where is it produced? What is the stimulus for ANP secretion? What are the actions of ANP? (Fig. 20- 11) 20.26 Hyperkalemia (increases/decreases?) the K+ concentration gradient across cell membranes and (depolarizes/hyperpolarizes?) cells. This leads to (increased/decreased?) excitability in excitable tissues and can lead to cardiac arrhythmias. Compare this to hypokalemia. 20.27 How does the body compensate for increased K+ levels? 20.28 Which receptors trigger thirst, and what is their threshold osmolarity? 20.29 What effect does severe dehydration have on GFR? ☞༅ Be able to complete a reflex pathway for any hormone in this chapter! ☞༅ Look the chart in Fig. 20- 12 that represents the possible disturbances of volume and osmolarity and for each disturbance, be able to map the appropriate homeostatic response. 71 CH 20 PROBLEMS - FLUID AND ELECTROLYTE BALANCE ✔ Explain mechanistically why Na+ is the primary ion involved in the regulation of extracellular fluid volume. ✔ Arrange the following terms into a map of the RAAS pathway. (Fig. 20- 10) adrenal cortex angiotensinogen aldosterone JG cells angiotensin converting enzyme (ACE) liver angiotensin I (ANGI) plasma protein angiotensin II (ANGII) renin ✔ For either vasopressin or aldosterone, draw a picture of its action at a target cell, showing: a) the hormone receptor in the correct location, plus any details you know about the receptor b) whatever you know about the hormone’s intracellular signal pathway c) the cellular effect of the hormone’s action Be as complete and detailed, with clear labels of all elements, including body compartments. ✔ For any hormone and for renin, be able to name the cell or tissue (whichever is most specific) that secretes the molecule and write out the full reflex pathway. This icludes target cells/tissues, and the function or effect as asked. Be complete and as specific as possible. (Hormone effects may be cellular, tissue- level, or systemic.) ✔ Write out the full names for all acronyms and abbreviations. Spelling counts! 72 RENAL PROBLEMS 1. Systemic arterial blood pressure rises to a mean of 120 mm Hg (average mean = 93 mm Hg). Before any compensation takes place, what happens to the following in a nephron of the kidney? a) pressure in the afferent arteriole ___________________________________________________ b) blood flow in the afferent arteriole ________________________________________________ c) resistance in the glomerulus ______________________________________________________ d) GFR ________________________________________________________________________ 2. GFR is normally constant over mean arterial blood pressures from 80- 180 mm Hg. (a) What happens to GFR if mean arterial pressure goes from 120/80 to 100/65? _____________________________ (b) Tubuloglomerular feedback is a local mechanism that is used for this autoregulation of GFR. Fluid flow through the nephron is monitored by cells that release a paracrine that acts primarily on the afferent arterioles. If mean arterial pressure goes from 103 to 116, tubuloglomerular feedback will cause the arterioles to ________________________. 3. If the urine concentration of inulin is 29 mg/mL, urine flow is 1.1 mL/min, and plasma inulin is 0.25 mg/mL, what is the GFR? 4. List one substance for which clearance by the human kidney is approximately: zero: _______________________________ 100% _______________________________ 5. You need money to go to South Padre for Spring Break, so you volunteer to be part of a Pharmaco study on how the body handles a new drug, miracure. You are administered a dose of miracure intravenously. Blood and urine samples are collected with the following results: 24 hour plasma level 24 hour urine sample (Volume = 1.5 L) miracure 2 mg/dL miracure 3.022 g creatinine 1.2 mg/dL creatinine 2.016 g How does the human kidney handle miracure? 73 _______________________________________________ 6. Thirsty student drank 1.5 L of water. For the primary hormonal compensation for this condition, what is the Integrating center Efferent One specific effector One specific effect Overall effect 7. Compare the following pairs of items. In all situations, assume all other factors to be equal and the conditions given are the only under consideration. Put one of the following symbols in the space given: > (greater than) < (less than) = (same as or equal) GFR when BP = 120/80 _______ GFR when BP = 175/110 osmolarity of filtrate at end of _______ osmolarity of plasma in peritubular capillaries proximal tubule radius of afferent arteriole with Epi _____ radius of afferent arteriole with norepinephrine 74 Discussion Exercise—Renal epithelial transport 1. Create an epithelial model of reabsorption using these transporters: Na+/K+ ATPase Na+ channel Na+/Glu symporter How is the reabsorption of these substances linked to Na+ reabsorption? H2O, urea, Cl- Apical Proximal Tubule cell Basolateral 2. Secretion involves movement of substances in reverse of reabsorption, from the plasma to the lumen; however the mechanisms are similar. Major substances secreted are H+, K+, organics Create an epithelial model of secretion using these transporters: Na+/K+ ATPase Na+/organics antiporter K+ channel Na+/H+ antiporter Apical Basolateral Proximal Tubule cell 75 Discussion Exercise—Renal Math 1. A patient experiencing an increase in urine output among other symptoms consulted an internal medicine spet. The spet ran a number of tests related to renal function. Here are some of the results. Urine flow = 2 L/day Be sure to watch units! Plasma [creatinine] = 0.1 mg/dL urine [creatinine] = 75 mg/L Plasma glucose = 400 mg/dl urine [glucose] = 37.5 g/L a. Use creatinine clearance to estimate the patient’s GFR. b. How much glucose does the patient filter per day? c. How much glucose does the patient excrete per day? d. What is his transport maximum in mg/day? e. What is the patient’s renal threshold? f. Calculate the patient’s glucose clearance. What is normal glucose clearance? (see text) 76 CHAPTER 20 READING QUESTIONS - ACID- BASE BALANCE 20.31 Define pH in words and mathematically. 20.32 A change of 1 pH unit = a ________- fold change in H+. 20.33 An alkaline solution has a (higher/lower?) H+ concentration and a (higher/lower?) pH than an acid solution. 20.34 What is the normal average pH and the normal pH range of the human body? 20.35 Which body fluid is used clinically to indicate the body pH? 20.36 Pathological pH values disrupt what physiological functions? 20.37 The biggest daily source of acid production is _____________. 20.38 What enzyme catalyzes the production of H2CO3 from CO2 + H2O? 20.39 Name the three mechanisms used by the body to cope with minute- to- minute changes in pH. List the order in which these mechanisms are employed—which is the first line of defense, second, third … and explain why. 20.40 What is a buffer? List some important buffers found in the human body. 20.41 Which is the most important extracellular buffer? Where does it come from?(Fig. 18- 11) 20.42 What effect does an increase in (H+) due to production of metabolic acids have on pH, HCO3, and CO2? 20.43 Sometimes changes in plasma HCO3 concentrations aren’t observed clinically. Explain why this is true. 20.44 If ventilation increases, what happens to plasma PCO2, H+, and HCO3 ? 20.45 If ventilation decreases, what happens to plasma PCO2, H+, and HCO3 ? 20.46 The body uses ventilation as a method for adjusting pH only if a stimulus associated with pH triggers the reflex response. Name the two stimuli that can do this and their sensors. 20.47 How do the kidneys respond in times of acidosis? (Fig. 20- 16, 20.17b) 20.48 What substances act as buffers in the kidneys? 20.49 How do the kidneys respond in times of alkalosis? 20.50 Renal compensations are (faster/slower?) than respiratory compensations. Why? 20.51 Outline, diagram, or describe how bicarbonate is reabsorbed and H+ secreted in the proximal tubule. 20.52 How do I cells compare to P cells? What does “I” stand for here? 20.53 Diagram, outline, or describe how type A and type B cells work. Include the transporters and ions involved. (Fig. 20- 17 a,b) 20.54 How are acid- base disturbances related to K+ balance? Discuss transporters and acid- base states when answering this question. 20.55 Name the four major acid- base disturbances. (Table 20- 2) 20.56 If the problem is of respiratory origin, what homeostatic compensation is available? 20.57 In metabolic acid- base disturbances, what homeostatic compensation is available? 20.58 What alteration in ventilation will cause a respiratory acidosis? 20.59 Name some causes of metabolic acidosis. 20.60 The hallmark of metabolic acidosis is _____. What compensation mechanisms are available in this state? Because compensation is almost instantaneous in this condition, the PCO22 levels will often be (greater than/less than/the same as?) normal. 20.61 Respiratory alkalosis occurs as a result of ______. 20.62 What could cause metabolic alkalosis? 20.63 What compensation mechanisms are available for each type of alkalosis? 77 20.64 To distinguish a respiratory acidosis from a respiratory alkalosis, you should look primarily at the relative concentrations of (H+/CO2/HCO3?). 20.65 To distinguish a respiratory acidosis from a metabolic acidosis, you should look primarily at the relative concentrations of (H+/CO2/HCO3?). 20.66 To distinguish a respiratory alkalosis from a metabolic alkalosis, you should look primarily at the relative concentrations of (H+/CO2/HCO3?). List the four types of simple acid- base disturbances. For each disturbance, use the equation CO2 + H2O ⇄ HCO3- + H+ to predict what happens to CO2, HCO3- , and H+. A. ____________________________________________________________________ CO2 increased decreased within normal limits HCO3- increased decreased within normal limits H+ increased decreased within normal limits B. ____________________________________________________________________ CO2 increased decreased within normal limits HCO3- increased decreased within normal limits H+ increased decreased within normal limits C. ____________________________________________________________________ CO2 increased decreased within normal limits HCO3- increased decreased within normal limits H+ increased decreased within normal limits D.. ____________________________________________________________________ CO2 increased decreased within normal limits HCO3- increased decreased within normal limits H+ increased decreased within normal limits ✔ If the pH range compatible with life is 7.0- 7.7, how can we survive stomach juices with a pH as low as 1 or urine with a pH ranging from 4.58.5? 78 ✔ ♢ Fill in the following table with the respiratory reflex pathways that are triggered by metabolic acidosis. Be AS SPECIFIC and DETAILED AS POSSIBLE when describing various parts of the pathway. (Example: "glomerulus" is more specific than "kidney.") Include neurotransmitter/receptor where appropriate. Stimulus Sensor(s) Afferent pathway(s) Integrating center(s) Efferent pathway(s) Effector(s) Response of effectors Net result of reflex pathway metabolic acidosis (Circle one) ventilation increases / decreases 79 ACID BASE BALANCE PROBLEMS 1. Match the four conditions at the left to the appropriate acid- base disturbance on the right. a) [H+] elevated, HCO3- low compensated metabolic acidosis ______ b) pH elevated, HCO3- elevated uncompensated respiratory alkalosis ______ c) pH low, HCO3- elevated compensated metabolic alkalosis ______ d) [H+] low, HCO3- low uncompensated respiratory acidosis ______ 2. More acid- base disorder matching. Which disorder(s) is caused or characterized by . . . A = All disorders B = respiratory alkalosis C = metabolic alkalosis D = Respiratory acidosis E = metabolic acidosis N = none denaturation of proteins hyperkalemia elevated bicarbonate diarrhea respiratory compensation high CO2 & high bicarbonate 3. Patient 1 is breathing rapidly upon arrival. Labwork shows the following: PCO2 = 35 mm Hg, pH = 7.27, HCO3- = 18 meq/L. a. Is this patient’s hyperventilation cause or compensation for his acid base disturbance? Circle one: cause compensation impossible to tell b. For this patient’s hyperventilation, an upregulation of quiet respiration, list stimuli Integrating Center Receptor(s) Efferent: One effector 4 a. Which curve shows the effect of acidosis on the HbO2 curve? Circle one: curve 1 curve 2 b. Circle all other facts that have a similar effect on the curve. anemia Hypoxia hyperthermia hypocapnia (CO2) 1 c. How does severe acidosis affect gas transport? Be specific! 2 Discussion Exercise: Acid- Base problems 1. Use the information for each patient to from that of what the acid- base disturbance is. Be able to d How is the effect of CO poisoning different determine explain your rationale for each. severe acidosis? 80 Discussion Exercise: Acid- Base Problems 1. Use the information below for each patient to determine what the acid- base disturbance is. Be able to determine is. Be able to explain your rationale for each. Normal values: pH = 7.40; [HCO3-] = 24 meq/L; PCO2 = 40 mm Hg pH [HCO3- PCO2 Diagnosis a. 7.34 15 29 b. 7.49 35 48 c. 7.62 20 20 d. 7.47 14 20 e. 7.26 26 60 2. A previously healthy man develops a gastrointestinal illness with nausea and vomiting. After 24 hrs of illness, he is sent to the lab for tests. When the illness continues, he is sent back a second time. The data from the two lab visits are shown below: 24 hrs 60 hrs Body weight 70 kg 68 kg Blood pressure 110/70 80/40 Plasma pH 7.5 7.48 Arterial PCO2 44 mm Hg 48 mm Hg Plasma [HCO3- 32 meq/L 30 meq/L Urine pH 7.5 7.6 81 a) What is his acid- base disorder and what is its origin? b) What has happened to acid- base disturbance by 60 hrs? c) What are the homeostatic compensations for this acid- base disturbance? d) Map the renal- related compensations for his decrease in blood pressure. 82 CHAPTER 21 READING QUESTIONS - GI 21.1 What is the function of the GI tract? 21.2 List two important challenges the GI tract must overcome to carry out this function. 21.3 List and define the four basic processes of the digestive system. (Fig. 21- 2) 21.4 What happens to nutrients brought into the body through the digestive system? 21.5 Why does the digestive system include the largest collection of lymphoid tissue in the body? 21.6 What is the name given to the GI system’s immune tissue? 21.7 Summarize mass balance in the digestive system. (Fig. 21- 1) 21.8 Trace a piece of food that enters the mouth through the digestive system, and follow its undigested portion until it is excreted. Include the sphincters the food passes. (Fig. 21- 3) 21.9 The tubular invaginations of the lumen that extend into supporting connective tissue are called _______________________________ in the stomach and ___________________________ in the small intestine. 21.10 What are the two purposes served by GI motility? 21.11 Most of the intestinal tract is composed of _____________________- unit smooth muscle whose cells are electrically connected by ___________________________ junctions. (See p. 427.) 21.12 List the sources and volumes of fluid input into the GI tract. (Fig. 21- 1) 21.13 List the five major ions found in digestive secretions 21.14 List the structures that secrete digestive enzymes. 21.15 Enzymes secreted in inactive form are known collectively as ___________________________. 21.16 What are the roles of the liver in digestion? (Fig. 21- 6) 21.17 What are the key components of bile? What is the relevance of each component? (Fig. 21- 9) 21.18 Describe the role of the autonomic influence in long reflexes (Fig 21.11) 21.19 The primary responses controlled by the ENS are related to what functions? 21.20 What do the following abbreviations stand for? (Table 21- 1) CCK _________________________________________________ GIP __________________________________________________ GLP- 1 ________________________________________________ 21.21 Where are the following GI peptides synthesized/secreted and what is their function? gastrin _________________________ secretin __________________________________ CCK __________________________ GIP ______________________________________ GLP- 1 __________________________ 21.22 Where does most nutrient absorption take place? 21.23 Why is it necessary to emulsify fats during the digestive process? 21.24 Where does most water absorption take place? 21.25 What is the role of the hepatic portal system? ✔ Why don’t the powerful proteolytic enzymes of the pancreas digest the cells that secrete them? ✔ Fill in the following table: Enzyme Digests ... Into ... Location(s) where secreted 83 amylase triglycerides pepsin maltase endopeptidase sucrose lactose trypsin CHAPTER 22 READING QUESTIONS 22.1 Explain what is meant by “energy balance” in the body. 22.2 Define metabolism. 22.3 Distinguish between anabolic and catabolic pathways. 22.4 What three possible fates do biomolecules meet in the body? 22.5 What are nutrient pools? (Fig. 22- 3) 22.6 Define and distinguish between the following terms: – glycolysis / glycogenesis / glycogenolysis / gluconeogenesis – lipogenesis / lipolysis – deamination / transamination 22.7 Review Fig. 22- 5 to examine the biological pathways important for energy production and how they interact. See Chapter 4 for detailed energy pathways. 22.8 Review the fates of nutrients during the fed state as outlined in Table 22- 5b. 22.9 What are the potential fates for absorbed glucose? amino acids? lipids? 22.10 Once in the bloodstream, how are triglycerides converted into free fatty acids and glycerol? 22.11 How is unused glucose stored? unused amino acids? unused fats? 22.12 What is the signal for a shift in metabolic state? 22.13 What is the goal of the fasted state? 22.14 Which organ is the primary source of glucose production during the fasted state? (Fig. 22- 8) How does it contribute to available glucose levels? 22.15 What are other sources of energy during the fasted state? 22.16 What is beta- oxidation? What are the potential dangers of beta- oxidation? 22.17 Hour- to- hour regulation of metabolism depends on what ratio? 22.18 Which hormone is dominant during the fed state (Fig. 22- 14a)? What is the net metabolic effect? 22.19 Which hormone is dominant during the fasted state (Fig. 22- 14b)? What is the net metabolic effect? 84 22.20 List and briefly describe the factors that influence insulin secretion: 22.21 Distinguish between type 1 and type 2 diabetes mellitus. 22.22 How is diabetes characterized? What are some of the causes of diabetes? 22.23 Explain the physiology behind each of the symptoms of untreated type 1 diabetes mellitus (Fig. 22- 20): glucosuria, ketone production, muscle wasting, metabolic acidosis, polydipsia, polyphagia, osmotic diuresis, hyperglycemia, increased ventilation, hyperkalemia 22.24 What are the treatment options for type 1 diabetes mellitus? ✔ What is the calorie content of the following food, and what percent of the calories come from fat? Spaghetti and Meat Balls: Fat 6 g Carbohydrate 30 g Protein 8 g ✔ What does insulin do to: glycolysis? ___________________________________________________ gluconeogenesis? ___________________________________________________ glycogenesis? ___________________________________________________ lipogenesis? ___________________________________________________ protein synthesis? ___________________________________________________ ✔ ♢ Name the cell that secretes insulin. Be as complete and specific as possible. CHAPTER 23: ENDOCRINE ADRENAL CORTICOSTEROIDS ✔ Why is cortisol considered to be a catabolic hormone? Give examples to support your answer. ✔ Draw a map for cortisol. Include the following terms. Add additional terms as desired. ACTH CRH anterior pituitary HPA pathway corticosteroid- binding globulin hypothalamus corticotropin melanocortins cortisol pro- opiomelanocortin THYROID HORMONES Use the following symbols and fill in the blanks: greater than (>), equal to (=), or less than (<) ✔ A person who has a pituitary endocrine tumor that is causing hypersecretion of all adenohypophyseal hormones could be expected to have the following hormone levels: Cortisol would be ______ normal. CRH would be ______ normal. ACTH would be ______ normal. ✔ A person taking exogenous thyroid hormone in an illegal diet pill would have the following hormone levels while taking the diet pill: TRH would be ______ normal. TSH would be ______ normal. 85 METABOLISM AND DIGESTION PROBLEMS 1. T/F/correct. If statement is true, write true in blank. If false, write a term in the blank that will make the statement true by replacing the underlined term. Hypoglycemia causes the liver to release glucagon, which acts to raise plasma glucose. Insulin stimulates glycolysis and gluconeogenesis in liver cells. Drugs that open K+ATP channels cause pancreatic beta cells to hyperpolarize and release less insulin. 2. In Crohn’s patients, malabsorption of nutrients is so severe as to mimic starvation. In addition, they often stop eating because of the unpleasant consequences of eating – cramping, diarrhea, reverse peristalsis, etc. Thus, their plasma levels of nutrients are very low. Based on this information alone, what change from normal would occur in the following parameters? Use arrows for increase/decrease and nc for no change. _____Plasma [insulin] _____ Formation of glucose from amino acids _____Glycogenesis _____ plasma fatty acids _____Activity of pancreatic α (A) cells _____ Plasma [cortisol] _____# Glucose transporters in brain _____ Formation of muscle protein _____ ketogenesis _____ uptake of glucose by adipose 3 In the questions below, fill in the blanks with one of the following: increased /greater than unchanged /the same as decreased /less than a) Insulin secretion after glucose is given intravenously will be _________ compared to insulin secretion after the same amount of glucose is given orally. b) The number of GLUT transporters on skeletal muscle cell membranes following insulin injection will _________. c) The number of GLUT transporters in membrane of intestinal cells will _______following an injection of insulin. d) Renal reabsorption rate of glucose of an untreated diabetic (plasma glucose elevated) is ___________ the renal reabsorption rate of glucose in a normal individual with the same plasma glucose concentration. 4. Jan’s father had a thyroidectomy in 1987 due to thyroid cancer. At first he was given too much synthetic thyroid hormone (synthroid). a) Explain why he lost weight and became heat- intolerant. 86 b) Could the hyperthyroidism due to synthroid be considered a secondary pathology? Why or why not? c) Could a person develop goiter from administration of excess synthroid? Why or why not? 5. Some chemicals are so potently toxic that the mere taste can trigger a reflex leading to reverse peristalsis (vomiting). For this reflex, what is the: Receptor First integrating center First efferent nd 2 integrating center (be specific) Effector 6. Matching—Gastrointestinal C = carbohydrate P = protein F = fat A = all (relates to digestion of all macromolecules) N = none More than one answer may be possible. _____ digestion products are primary stimulus for the release of gastrin _____ mechanical digestion increases surface area _____ absorption of digestion products is by simple diffusion _____ digestion /absorption enhanced by sympathetic input _____ stimulates release of secretin _____ enzymatically digested by brush border enzymes _____ absorption is hormonally regulated _____ the chief cells are involved in optimal digestion of this macromolecule 87 88 Answer Key for Numbered Problems Membrane and Epithelial Transport 1. Which means of membrane movement are concentration- dependent? a, b, f require ATP? c, d, e, f require some input of energy other than molecular motion? c, d, e, f can be saturated? b, c, d (receptor- mediated), f require a membrane protein? b, c, d (some forms), f will show competition? b, c, d (R- mediated), f are associated with membrane vesicles? d, e have rate dependent on membrane surface area? a (d, e—ok) 2. Ca2+: 3H. K+: 4G. Steroid: 1F 3. Na+- K+- ATPase = B, C, D. Na+- glucose transporter =A,D,E. Ca2+- ATPase = C. GLUT transport = F. 4. a) decreases b/c no Na+ to run the symporter and bring glucose into the epithelium b) does not change b/c Na on BL side is funtionally impermeable. Not needed for any part of the process. c) Nothing happens to Vm..Membrane is impermeable. 5. a) emphysema causes loss of surface area for diffusion to occur across b) fibrosis involves formation of scar tissue that increases diffusion distance 6. Active protein- mediated; ICF more concentrated than ECF; active transport necessary to concentrate a substance. The graph does not illustrate saturation of transport, but rather a steady- state situation where ICF glucose has stabilized. A saturation graph would have rate of transport on the y axis. 7. apical Basal 8. absorption H+ - Fe++ symporter On apical membrane Fe & H both move into cell H+ - Na+ antiporter On apical membrane H moves out, Na moves in Fe++ transporter (ferroportin) On basal membrane, Fe moves out Na+- K+ ATPase On basal membrane, K moves in, Na moves out 89 9. a. apical b. basolateral c. Mammary cell is moving Ca2+ from ECF into duct in order to produce milk (net secretion) Ca2+ concentration is higher in ECF than in cell; needs only passive transport in order to move in. d. on the apical membrane e. domain- specific transport proteins, maintained largely by tight junctions Solutions, Osmolarity and Tonicity 1. 10 g glucose into 200 mL final volume 2. 2.7 g NaCl into 300 mL final volume 3. The total concentration of the resulting solution is 1.667 M. The final concentration of NaCl is 0.667 M or 1.333 OsM. The final concentration of glucose is 1 M or 1 OsM. 4. 0.9 g/100 mL = 9 g/L x 1 mole/58.5 g = 0.154 mole/L x 1.8 osmoles/mole = 0.277 OsM 5. 278 mOsM glucose + 138 NaCl = 416 mOsM 6. a) 600 mOsM NaCl – shrinks b) 600 mOsM urea - swells (hemolyzes) c)–shrinks 7. a) 600 mOsM NaCl is __hyper_osmotic and ___hyper__tonic to the cell. b) 600 mOsM urea is __hyper_osmotic and ___hypo_tonic to the cell. c) 300 mOsM urea/300 mOsM NaCl is __hyper_osmotic and ___iso_tonic to the cell. 8. – 1 mL x 5 mg/mL = 5 mg administered – plasma has inulin content of 0.001 mg in 2 mL 5 mg/ ? mL = 0.001 mg/ 2 mL The 5 mg is distributed in 10 L – Inulin is the marker for the ECF. If total body volume is 27 and ECF is 10 L, ICF = 17 L. – Two acceptable answers for IF volume. Best one is that you do not have info to calculate IF (would need plasma volume). Can also estimate that IF is 75% of ECF. 9. False. All hyposmotic solutions are hypotonic. 10. 300 mOsM NaCl and 300 mOsM urea What happens to ICF volume? no change What happens to ICF osmolarity? up What happens to ECF volume? up (the IV has to go somewhere!) What happens to ECF osmolarity? up 90 11. a) Ingest 1.5 g LiCl: ECF vol inc., ECF osm. inc., ICF vol. dec., ICF osm. inc. b) IV of 300 mOsM LiCl/50 mOsM urea: ECF vol. inc, ECF osm. inc, ICF vol. no change, ICF osm. inc. 12. You have to use some but not all information. Normal TBW is 60% of total body weight. Dehydrated body water is not the same percentage! Assume all solute loss comes from the ECF. This does NOT mean that all volume lost came from the ECF. If you lose a dilute fluid from the ECF, the osmolarity of the ECF fluid left behind will increase. This will cause water to shift out of the cells, so ICF volume also goes down. a) The solution you want to make up will be: e) hyposmotic and hypotonic If osmolarity goes up, you have lost water in excess of solute (a hyposmotic fluid). You always want to try to replace what was lost. Rule you should learn: a hyposmotic solution is ALWAYS hypotonic. b) The replacement solution will be 6 L (vol) and have a concentration of 108 mOsM. (You do not need to do the ECF and ICF values to answer this question.) See charts. Normal Dehydrated Total Total solute S = C x V = 11.952 osmoles solute 12.600 osmoles volume 42 - 6 = 36 L volume 42.000 L conc 0.332 OsM conc 0.300 OsM He lost 6 kg which is equivalent to 6 L fluid loss. You now know C and V and can calculate solute remaining. He lost [normal - dehydrated] solute, or 0.648 osmoles. 0.648 osmoles in 6 L replacement volume = 108 mOsM Communication/Reflex Pathways/Endocrine 1. Stimulus = decreased Ca. Receptor/IC = parathyroid cells. Efferent path = PTH. Effectors = kidney and bone. (Tissue) response = incr. reabsorption and incr. release of Ca. 2. (in order) S, S, P, S, P, S, N, B 3. (in order) A, S, P 4. see Fig. 23.5 5. in order: N, A, B 6. secondary; begins with low TSH causing low T4. Reduced negative feedback from T4 causes TRH to be elevated 7. first integrating center hypothalamus final integrating center thyroid first efferent TRH final efferent T3/T4 thyroid hormones 8. simple diffusion 9. a. 91 10. a. circle b. primary- - The high T4 corresponds with low TSH indicating that the elevated T4 begins with the thyroid and exerts negative feedback on the trophic hormones. 11. c. Neurophysiology 1. pregangl. autonomic= ACh on N. Symp= NE on alpha and beta (1 only). Adrenal medulla= E on alpha and beta (1 and 2). Somatic motor= ACh on N. 2. h - - autonomic & sympathetic 3. a) Acetylcholine on nicotinic R. b) norepinephrine on α, β1 R (adrenergic) c) targets: cardiac, smooth muscle, glands 4. a) P, b) N, c) B, d) B, e) B, f) S, g) S 5. Extracellular [K+]4 to 6 mM = a) membrane depolarizes Extracellular [Na+] 135 to 137 mM = c. resting membrane potential does not change significantly [resting cell is functionally nonpermeable] Membrane permeability to K+ (PK) increases = b. membrane hyperpolarizes Membrane permeability to Na+ (PNa) increases = a) membrane depolarizes 6. False. The membrane potential (difference) will decrease because the Na/K pump is electrogenic and has a slight hyperpolarizing effect so, if blocked, cell will depolarize somewhat. However, membrane potential is largely established by passive distribution of ions. (Note: blocking the pumps will eventually have detrimental effects on many aspects of cell function, but question asked for immediate effects). Cardiovascular 1. Answer: Flow A>Flow B Flow A = 125- 75/R R = 16/24 ≅ 1 (ignore the constants) therefore flow ≅ 50 (R can be expressed in mm Hg/vol/time, so flow units come out in vol/time) Flow B = 80/2 = 40 2. b. decrease by half (inversely related) 3. a. 1/5000th 4. a. false. Velocity of flow is lowest...b. teleological; Velocity of flow is lowest in capillaries because total cross- sectional area is greatest, and driving force per particle is less. 5. heart pumps about 273 kg/hr or 600.6 lb/hr 6. MAP is 68.3 mm Hg; pulse pressure is 25 mm Hg. You can't calculate CO unless you use an estimated value for stroke volume. 7. A failing left ventricle is the most common kind of heart failure. The difference in CO between the right and left ventricles is 42 mL. This blood will pool in the pulmonary circulation. 8. Pacemakers: innervated by the vagus nerve; slow depolarization to threshold; no high resting permeability to any one ion; regulate rate of heart beat; Ca2+ action portentials 9. (complete heart block) d) Conduction of action potentials through the ventricles appears to be normal. 92 10. SA node normally sets the pace because b. it depolarizes at fastest rate. Since there is no P wave in trace 1, and the P wave occurs after the R wave and is inverted in trace 2, it appears that the AV node is the ectopic pacemaker (firing out of turn) 11. the electrical activity is going the opposite direction of the lead. 12. AV valve closure PR segment T wave ventricular relaxation Signal through intermodal pathways signal through atrial contractile cells (carries the signal to the atrial contractile cells) Na+ movement in contractile cells R wave Heart sound 2 ST segment—precedes relaxation & valve closure (following blood movement from the vena cavae:) Blood movement through pulmonary arteries through pulmonary veins 13. (if diameter is 1/3 of normal, then r is 1/3 also) Flow ∝ Δ P/R R ∝ 1/(1/3r)4 therefore R increases 81 x and Flow decreases 81 x 14. gap junctions 15. a. arrhythmia = irregular heart beat; A fib and v-fib b. contractile cell c. openended Respiratory 1. Answer: less than 137 mm Hg. Water vapor P of 47 subtracts from Patm, not just from PO2. (700 – 47) x 21% = 137 mm Hg PO2. That is air entering lungs. But it will mix with “old” air in lungs, diluting the oxygen. 2. a. MVV = VC x breathing rate ( similar to Total pulmonary ventilation) Note that tidal volume can range from a resting breath all the way to vital capacity b. Alveolar = (VC – DS) x breathing rate = (5.2 – 0.2L) x 25 br/min = 125 L/min c. V = Alv ventilation = 125 L/min P = CO = HR x SV = 25 L/min therefore V/P = 125/25 = 5 d. 5 >>> than the desired 0.8….main problem is severely decreased plasma CO2 (can lead to respiratory alkalosis) 3. Airway resistance high ACh > Airway resistance with low ACh TPP in pneumothorax < TPP at end of normal expiration Bronchiolar diameter if alveolar PCO2 = 40 < Bronchiolar diameter if PCO2 = Total lung capacity > forced vital capacity Alveolar PCO2 > atmospheric PCO2 TPP at end of expiration < TPP at end of inspiration Intra- alveolar pressure > intrapleural pressure Intrapleural pressure at end of inspiration< intrapleural pressure at end of expiration 93 4. Neurotransmitter Receptor subtype Effector(s) Phase 1 ACh (parasymp) muscarinic Bronchiolar smooth muscle Phase 2 ACh nicotinic Internal intercostals abdominals 5. 50% (Note that water vapor pressure is part of the total pressure. Usually we calculate %O2 in “dry” air. The typical 20- 21% is in dry air. Which is why the water vapor pressure must be substracted from total atm press before multiplying by 20- 21%) 6. Answer: 1.4 mL O2/g Hb HbO2/dL =( % Sat) (max capacity)(g Hb/dL) 18.7 mL/dL = 0.99 * max capacity * 13.5 g/dL solve for max capacity Integrated Cardiovascular & Respiratory Questions 1.__1___Conduction through AV node _____ conduction through Purkinje fibers __1___conduction through right bundle branch __1___ conduction through left bundle branch ___1__QRS wave ____ right ventricular systole __1___decrease in transpulmonary pressure _____ movement of air out of the lungs 2. Cardiovascular Respiratory site of variable resistance arterioles bronchioles site of highest resistance aorta trachea location of pacemaker SA node medulla oblongata Neural control of resistance sympathetic (inc. art. para (inc. bronchiolar resistance) Resist) muscle type of pump cardiac skeletal CNS control center medulla medulla and pons effect of low interstitial oxygen vasodilation vasoconstriction 94 3. Receptor B2 Muscarinic NT or NH Epi ACh B1 Norepi B2 Epi Tissue Response Bronchiolar smooth muscle bronchodilation SA node Increased K+ permeability; decreased rise of prepotential ventricles Increased cAMP, inc. intracellular Ca2+ & force of contraction Arteriolar smooth muscle Vasodilation alpha Norepi Arteriolar smooth muscle vasoconstrict 4. Heart rate when R- R interval is 0.75 sec=80 heart rate when R- R interval = 0.5 sec =120 Transpulmonary pressure at end of inspiration(+6) TPP at end of expiration (+3) Total pulmonary ventilation with 12 breaths/min alveolar ventilation with 12 breaths/min MAP, if systolic = 140, diastolic = 90 =107 pulse pressure (systolic = 140, diastolic = 90)=50 Normal intrapleural pressure - 3 intrapleural pressure in pneumothorax=0 = Bronchiolar diameter with ↑ ACh- - constrict bronchiolar diameter with ↑ CO2 dilate Use of internal intercostals due to fibrosis use of internal intercostals due to emphysema (Forced expiration) % saturation in anemia due to blood loss % saturation in CO poisoning Conduction velocity through AV node conduction velocity through Purkinje fibers 5. Respiratory bronchioles Total pulmonary ventilation Effect of Epi on β2: bronchodilate Role of elastin—to generate: Intra- alveolar Pressure Residual volume Velocity of flow is lowest in the: Alveoli 6. bradycardia; a. acetylcholine Cardiovascular arterioles Cardiac output (L/min) Effect of Epi on β2: vasodilate role of elastin—to generate: diastolic Pressure End systolic volume Velocity of flow is lowest in the: capillaries 95 Renal 1. a) increases b) increases c) no change d) increases 2. GFR decreases, arterioles constrict 3. 127.6 mL/min 4. zero= glucose, amino acids. 100% = creatinine, inulin 5. How does the human kidney handle miracure? filters it with net reabsorption To answer this you needed to know that filtration rate of creatinine = excretion rate of creatinine, so you can use F = GFR x [creat] plasma to determine GFR. Or you can simply determine creatinine clearance. 1.2 mg Cr/100 mL plasma x GFR = Cr excretion (2016 mg/day x 1000 mL plasma/12 mg Cr) GFR = 168 L/day Clearance of miracure = 151.1 L … < GFR, therefore reabsorbed. 6. Integrating center Atrial myocardium Efferent ANP One specific effector JG cells, efferent arteriole, mesangial cells, adrenal cortex, hypothalamus One specific effect ↓renin, constrict, relaxà༎ ↑GFR, ↓ aldo, ↓ ADH Overall effect Na+ and water excretion 7. all are equal (=) Acid Base 1. a: compensated metabolic acidosis d: uncompensated respiratory alkalosis b: compensated metabolic alkalosis c: uncompensated respiratory acidosis 2. A denaturation of proteins D & E hyperkalemia (type A cells) D & C elevated bicarbonate E diarrhea (lose bicarb) C & E respiratory compensation D (C ok) high CO2 & high bicarbonate 3. a. compensation; if it were cause, then pH would be high (H+ low) b. stimuli high H+ à༎ high CO2 Integrating Center the DRG of the RCC Receptor(s)peripheral (carotid/aortic) and central (medullary) chemreceptors Efferent:somatic motor neurons One effector diaphragm/external intercostals/scalenes 4. a. curve 2 b. hyperthermia c. decreases O2 transport by decreasing O2 bound at lungs (also denatures proteins such as Hb) d. causes ↑affinity (left shift) at low PO2 e. none 96 Metabolism & Digestion 1. pancreas, glycogenesis, true, 2.. ___↓__Plasma [insulin] __↑___ Formation of glucose from amino acids ____↓___Glycogenesis _____↑_ plasma fatty acids ____↑__Activity of pancreatic α (A) cells ____↑_ Plasma [cortisol] __nc___# Glucose transporters in brain ____↓___ Formation of muscle protein __↑____ ketogenesis ___↓____ uptake of glucose by adipose 3. a) less than b) increase c) not changed d) equal to 4. a) Thyroid hormones increase metabolism, generating heat. They also stimulate catabolism of proteins and fats, thus the weight loss. b) No; a secondary pathology originates in the hypothalamus or ant. Pituitary. c) No; assuming that synthroid completely mimics thyroid hormones, then TSH would be suppressed due to negative feedback. Excess TSH causes goiter. 5. Receptor Taste buds First integrating center CNS First efferent Vagus/parasymp or symp neurons 2nd integrating center (be specific) Effector Myenteric plexus GI smooth muscle 6.. __P___digestion products are primary stimulus for the release of gastrin __A___ mechanical digestion increases surface area __F___ absorption of digestion products is by simple diffusion __N___ digestion /absorption enhanced by sympathetic input __N___ stimulates release of secretin __C,P___ enzymatically digested by brush border enzymes ___N__ absorption is hormonally regulated ___P__ the chief cells are involved in optimal digestion of this macromolecule ...
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