Case Teaching Notes for
“Agony and Ecstasy: A Case Study on Cell Membrane Structure and Function”

Introduction / Background

This case study is a “clicker case.” It combines the use of student personal response systems (clickers) with case teaching methods and formats. The case is presented in class using a series of PowerPoint slides punctuated by questions (called “clicker questions”) that students respond to before moving on to the next slide. In this way, students work through the material to understand (and usually also solve) the problem presented in the case. Specifically designed for use in large introductory science classes, the method integrates lecture material, case storylines, student discussion, (clicker) questions, clarification of answers to those questions, more lecture, and data.

The case is designed for an introductory biology course for either science or non-science majors but could be adapted for upper level courses. It uses an example of water intoxication to introduce membrane structure and function, osmosis, and electrolyte balance in the body. The premise of the case is a college student who, after taking the drug Ecstasy, begins to feel ill and is brought to a hospital where a new intern tries to determine what is wrong. The case provides a real-world connection in that many college students will know of or may have tried Ecstasy. In addition, there have been several highly publicized deaths from water intoxication in recent years, some of which have been reported to involve Ecstasy abuse.

Important Concepts

• When molecules are unevenly distributed, random motion results in a net flow of particles from areas of high concentration to areas of low concentration in a process called diffusion.

• Membranes are semi-permeable barriers that hinder the passage of polar and charged molecules. Most polar/charged molecules can only cross cell membranes with the help of highly selective transmembrane proteins. Small polar molecules, such as water, can slip across membranes without help, but only very slowly. Rapid passage of water across membranes is facilitated by aquaporin transmembrane proteins.

• Passage of hydrophilic molecules across membranes is facilitated by highly selective membrane transport proteins. Water molecules associated with solute molecules are unable to cross membranes either directly or via water-specific transmembrane channels. As a result of these interactions, differences in solute concentrations across a membrane can result in a net flow of water from areas of low solute concentration to areas of high solute concentration in a process called osmosis.

• Excessive water flow in either direction across a cell membrane can damage cells and tissues. Biochemical reactions inside of cells depend on appropriate concentrations of ions and other molecules in the cytoplasm which can be adversely affected by excessive water transport.

Objectives

• Students will understand what diffusion is and the physical mechanism that causes it.
• Students will understand which types of molecules can (hydrophobic) and can’t (hydrophilic) cross membranes very easily and the reasons for these differences.
• Students will be able to explain how water moves across a membrane (directionality) in response to different solute concentrations inside and outside the cell.
• Students will understand the dangers of insufficient and excessive hydration and their effects on living cells and tissues.

Classroom Management

This class can be taught in a single 75-minute class period. It assumes that students have already learned about the major macromolecules found in living organisms and concepts such as hydrophobicity/hydrophilicity and basic membrane organization. There are no pre-assigned reading materials for the case.

The case includes several animations found on the web and described below. I recommend that instructors play with the animations a little before trying to use them in class. Be sure you can run the animations, and that you understand exactly what they are trying to show.

Teaching the Case

Slide 1, Slide 2, and Slide 3: Introduce the problem. The students take the perspective of a new hospital intern who is trying to figure out what is wrong with a patient brought into the hospital. Routine questions from the intern reveal that the patient has taken Ecstasy and this quickly becomes the focus of her investigation of the illness. Emergency room mention: When a particular drug is mentioned during examination of a patient, it is recorded in the patient’s chart. This is because this drug may, though not necessarily, be associated with the patient’s condition.

Slide 4: Provides a link to a website (http://thedea.org/MDMAatwork.html) that provides an animation describing the neurological/molecular mechanisms by which Ecstasy works. Essentially, Ecstasy alters the transport of the neurotransmitter serotonin across cell membranes resulting in abnormally high and persistent levels of signaling by this molecule.

Slide 5: Provides background information on Ecstasy and its physiological effects. Ask the students to read through the information and offer suggestions as to how Ecstasy might be making Brittany ill. Essentially, Ecstasy causes serotonin levels to remain for longer periods of time in the synapse, resulting in greater stimulation of serotonin receptors. This produces a high felt by users, but also affects other physiological processes.

Slide 6: Summarizes the various effects that Ecstasy has on the body.

Slide 7: Once the ways in which Ecstasy may be making Brittany ill have been determined, the intern orders medical tests. This slide gives the results of these tests.

Item and Measure	Normal	Brittany
Heart Rate (beats/min)	60–100	90
Blood Pressure (mmHg)	90/50 – 140/90	135/87
Temperature (°F)	98.6	100.2
Glucose (mg/dl)	60–109	72
Sodium—Na+ (mM/L)	135–146	115
Potassium—K+ (mM/L)	3.5–5.5	2.9
Chloride—Cl- (mM/L)	95–109	88
Oxygen—O2 (mmHg)	80–100	93
Carbon Dioxide—CO2 (mM/L)	22–32	24

Slide 8: Clicker question #1: Asks students to examine the data on the previous slide and suggest how Ecstasy might be making Brittany ill. This is a good time to bring up the concept of concentration and what it refers to, i.e., the amount of one substance (solute) dissolved in a given volume of another substance (solvent). Many students may be able to define “concentration,” but really don’t have a good grasp of what this concept means. In Brittany’s case, the solute would be ions and other electrolytes, and the solvent would be water.

Slide 9: Provides a diagram to explain to students what concentration refers to.

Slide 10: Continues the case after determining that Brittany is probably ill because her system has too much water. In order to understand why Brittany is having trouble, it is necessary for students to understand how molecules behave. More specifically, the movement of molecules is random. When molecules are distributed unequally in two areas, this random motion will lead to a net movement of molecules from the area of higher concentration to the area of lower concentration.

Slide 11: A link is provided to a website (http://physioweb.med.uvm.edu/diffusion/tocpage.htm) that provides good animations explaining diffusion (as well as osmosis). Your computer must be able to run JAVA to display the animations. Click on the tabs to the right to bring up different animations. Use the colored triangles to move between different animations under each section. It may be necessary to click in the animation to activate it.

The information provided in the text of the Lab Books website is more advanced than is probably appropriate for many introductory biology classes. It also gives a more specific definition of osmosis than the animations use to demonstrate some of the principles associated with osmosis. Use your own textbook to discuss osmosis at the appropriate level for your course.

Slide 12: Clicker question #2: Checks to see if students understand the basis of diffusion and random motion. The question asks students to submit an answer between 0–100%. If your clicker system only allows multiple-choice questions, answers for the students to choose from can be added to the slide.

Slide 13: Clicker question #3: Further checks to see if students understand the basis of diffusion and random motion.

Slide 14: Link to an animation: http://physioweb.med.uvm.edu/diffusion/tocpage.htm. After selecting the link, instructors will need to choose the appropriate animation from the list on the right side of the window.

Slide 15: Clicker question #4: Further checks to see if students understand the basis of diffusion and random motion by asking them to predict how they would expect a mixture of molecules to change over time.

Slide 16: Returns the students to the case by pointing out the conditions in Brittany’s body, namely, higher salt inside her cells than outside. Ask students to suggest what they think will happen. Some will erroneously say that salt will leave her cells because they will move from higher to lower salt concentrations. You will return to this issue a little later in the class. First, the students need to understand what types of molecules can/can’t cross membranes and why.

Slide 17: Clicker question #5: Introduces the idea of movement of hydrophilic versus hydrophobic molecules across the membrane. Students will often pick water because it is small. However, it is also polar. Hydrophobic molecules can interact with the hydrophobic tails of the membrane better and can cross more easily. Use the following slides to teach this concept

Slide 18: Describes the main concepts regarding what molecules can cross membranes. Hydrophilic molecules are unable to cross the membrane very well because they are unable to dissolve into the hydrophobic layer of the fatty acid tails. Water can cross, but only very slowly. Hydrophobic molecules, which can interact with the fatty acid tails, can generally cross without difficulty.

Slide 19: Explains how water is able to easily pass through the membrane in most cells in an animal’s body because of water specific channel proteins called aquaporins.

Slide 20: Brings students back to the situation in Brittany’s cells by providing a diagram showing the condition of the fluids inside and outside of Brittany’s cells. Essentially, through interactions with water and the aquaporin channel, solute alters the ability of water to pass through the channel. The overall result is that there is a net flow of water from areas of low solute concentration to areas of high solute concentration. Water flows in both directions, but there is a greater flow towards the higher solute concentration. The extent of this net flow is determined by the relative difference in the number of solute particles on the two sides of the membrane. The greater the difference in solute concentration on the two sides of the membrane, the greater will be the net flow of water. In the absence of other influences, a net flow will continue until the relative proportions of solute and water are the same on both sides of the membrane.

The movement of water in this manner may seem counterintuitive to some students. Many textbooks describe this as being due to the movement of “free” water molecules (i.e., not associated with solute). This explanation is overly simplified and incomplete. However, a more complete explanation would be more suitable for an advanced class. Additional information on the mechanism of osmosis can be found at:

• http://www.ucalgary.ca/~kmuldrew/cryo_course/cryo_chap4_2.html
• http://urila.tripod.com/index.htm
• http://physioweb.med.uvm.edu/diffusion/

Why are the water molecules organized the way that they are? This is a good time to remind students why water is a good solvent. Water is a polar molecule and the partial charges associated with the O and H interact with the (+) and (-) charges present on ions and other polar molecules.

Slide 21: Clicker question #6: Checks to see if the students understand the concepts covered in the previous few slides.

Slide 22: Provides a conclusion to the case describing Brittany’s prognosis. Brittany’s outcome would depend on how quickly the hospital treated her hyponatremia. Often this would include IV fluids containing normal or slightly higher sodium concentrations to correct the salt imbalance in her tissues. One of the primary problems associated with acute (sudden) hyponatremia, or water intoxication, is swelling of tissues due to osmotic uptake of water by cells. Though this occurs in all cells of the body, it is a particular problem in the brain because there is little room for the tissue to expand in response to the swelling. The resulting increase in intra-cranial pressure can cause severe brain damage and death as a result of herniation into the brain stem. The fact that Brittany was still conscious and was not experiencing seizures would suggest that she had not suffered brain damage yet and could still recover.

Textbooks often show animal cells lysing in the presence of too much water. However, this is unlikely to happen in a living animal. Instead, the primary problems faced by animals are swelling (as noted above) and changes in the concentrations of various solutes present inside of the cells. Solute concentrations that move outside of a relatively narrow range will interfere with delicate biochemical pathways. Disruption of critical biochemical pathways will kill an animal long before their cells actually lyse. Disruption of sensitive biochemical pathways is also a major problem associated with excessive dehydration.

Plants are limited to the water in their immediate environment and are more susceptible to severe shifts in water availability. As such, plant cells can experience severe swings in cellular water content. They also have mechanisms to help them withstand such swings. The cell wall prevents excessive swelling due to the presence of too much water. Plants can also use their large central vacuole to help maintain appropriate solute concentrations. That said, plant cells also can experience disruption of critical biochemical pathways due to excessive changes in solute concentrations in their cytoplasm.

Slide 23: Almost anything that can cause an electrolyte imbalance can potentially lead to acute hyponatremia. Most commonly, excess fluid loss (caused by diarrhea, vomiting, excess sweating, kidney problems, and certain medications) is replaced by water alone. In other cases, individuals take in an excess of fluids that are low in electrolytes over a short period of time. This has been seen in infants given inappropriate amounts of pure water or diluted formula and in adults drinking large amounts of beer (beer potomania). Recently, there have been several well-publicized cases of hyponatremia.

• Jennifer Strange died after a water-drinking contest “Hold Your wee for a Wii” sponsored by a local radio station in Sacramento in January 2007.
• Matthew Carrington, a Cal-State Chico student, died after fraternity hazing in February 2005.
• Washington D.C. police officer James McBride died while training for bicycle patrol in 2005.
• A 28-year-old runner Cynthia Lucero collapsed and died during the 2002 Boston Marathon.
• Brittney Chambers of Colorado (2001), Leah Betts of Great Britain (1995), and Anna Wood of Australia (1995) died after reportedly taking Ecstasy and drinking large amounts of water.
• Artist Andy Warhol died after hospital staff accidentally administered IV fluids that were too dilute following gall bladder surgery in 1987.

Slide 24: Reviews and defines movement of molecules across membranes so far. Ask students if there are other situations in which cells might want to move molecules that are different from these.

Slide 25: Describes active transport of molecules. Cells sometimes want to move molecules across the membrane against the concentration gradient. Examples might be food, such as glucose, moving into the cell. This process would require energy analogous to pumping water uphill requires energy.

Slide 26: Ask the student how cells might want to move large objects into the cell—they can’t fit through membrane channels.

Slide 27: Describes the process of exocytosis. Endocytosis is similar but reversed and with the endocytic vesicles usually fusing with lysosomes instead of the Golgi.

Assessment

This case was developed as part of an NSF-sponsored grant (# DUE 0618570) to determine whether clicker cases such as this one produced greater learning than the traditional lecture approach. As part of that project, assessment questions that can be asked before and after the class in which the material is presented were developed. The questions can also be used again during the final exam. These questions, along with their answers, are presented in the Answer Key.

Answer Key

Answers to the questions posed in the case study are provided in a separate answer key to the case. Those answers are password-protected. To access the answers for this case, go to the key. You will be prompted for a username and password. If you have not yet registered with us, you can see whether you are eligible for an account by reviewing our password policy and then apply online or write to answerkey@sciencecases.org.

References

Internet Sites

Information on water intoxication and hyponatremia:

http://www.nlm.nih.gov/medlineplus/ency/article/000394.htm

http://en.wikipedia.org/wiki/Water_intoxication

Information about Ecstasy and its effects:

http://www.nida.nih.gov/Infofacts/ecstasy.html

http://en.wikipedia.org/wiki/MDMA

Recent cases of water intoxication:

“Woman Dies after Water-drinking Contest”—http://www.msnbc.msn.com/id/16614865/

“A Fraternity Hazing Gone Wrong”—http://www.npr.org/templates/story/story.php?storyId=5012154

“District Officer Dies After Bike Ride”—http://www.washingtonpost.com/wp-dyn/content/article/2005/08/10/AR2005081001460.html

“Marathon Runner’s Death Linked to Excessive Fluid Intake”—http://www.remembercynthia.com/Hyponatremia_BostonGlobe.htm

“Hyponatremia (Water Intoxication)”—article about death of Leah Betts—http://thedea.org/hyponatremia.html

Articles

Robenson, J., Smollin, C., Sporer, K.A., Blanc, P., and Olson, K.R. 2007. Patterns of ecstasy-associated hyponatremia in California. Annals of Emergency Medicine 49(2): 164–171.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Pubmed&dopt=Abstract&list_uids=17084942

Article describing a possible association between Ecstasy use and the occurrence of hyponatremia.

Slide Credits

Unless specifically indicated otherwise below, all illustrations appearing in this case study were created by the author, Norris Armstrong.

Acknowledgements: This material is based upon work supported by the NSF under Grant No. DUE-0618570. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the NSF.

Date Posted: January 12, 2010.

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