Clinical Case Studies

Bad Fish: A Case Study on Nervous Tissue One evening during a recent trip to Indonesia, Dr. Marshall Westwood sat down to a meal of puffer fish and rice. Within an hour of returning to his hotel room, Dr. Westwood felt numbness in his lips and tongue, which quickly spread to his face and neck. Before he could call the front desk, he began to feel pains in his stomach and throat, which produced feelings of nausea and eventually severe vomiting. Fearing that he had eaten some "bad fish" for dinner, Dr. Westwood called a local hospital to describe his condition. The numbness in his lips and face made it almost impossible for him to communicate, but the hospital staff managed to at least understand the address he gave them and they sent an ambulance. As Dr. Westwood was rushed to the hospital, his breathing became increasingly labored. The patient presented in the ED with diaphoresis, motor dysfunction, paresthesias, nausea, and an ascending paralysis that started in his legs and spread to the upper body, arms, face, and head. The patient was cyanotic and hypoventilating. Within 30 minutes of presenting in the ED, Dr. Westwood developed bradycardia with a BP of 90/50 mmHg. Atropine was administered in response to the bradycardia. Intravenous hydration, gastric lavage, and activated charcoal followed a presumptive diagnosis of tetrodotoxin poisoning that was based on the clinical presentation in the ED. Five hours after treatment, the following vital signs were noted: - BP 125/79 mmHg - HR 78 bpm - Oxygen saturation: 97% on room air After discussing his case with his physician, he learned that he had probably been the victim of puffer fish poisoning. The active toxin in the tissues of this fish is a chemical called tetrodotoxin (TTX). Tetrodotoxin is in a class of chemicals known as neurotoxins because it exerts its effects on neurons. The specific action of tetrodotoxin is that it blocks voltage-gated sodium ion channels.

Short Answer Questions 1. Define the following phrases and terms associated with the signs and symptoms of Dr. Westwood's TTX poisoning: - diaphoresis - motor dysfunction - paresthesias - cyanotic - hypoventilating - bradycardia - gastric lavage - oxygen saturation 2. As mentioned in the case description, tetrodotoxin is a molecule that blocks voltage-gated sodium ion channels. What is a voltage-gated sodium ion channel and what is its function? 3. When nerve cells are at rest, there is an unequal amount of positive and negative charges on either side of a nerve cell membrane. This charge difference creates an electrical potential. Describe how the resting membrane potential (resting potential) is generated. 4. What is happening to the electrical potential of a neuron when it generates an action potential? What is the function of the action potential in neurons? 5. Describe the role of sodium ions and sodium channels in generating an action potential. 6. What would happen to a neuron if it was exposed to tetrodotoxin? Be specific regarding its effect on the ability of a neuron to communicate. 7. Now that you have addressed some of the basic biology of this case, explain why Dr. Westwood experienced numbness after eating the puffer fish meal. 8. Paralysis is a term used to describe the loss of muscle function. If tetrodotoxin's effect is on neurons, why did Dr. Westwood experience paralysis?

Angela's Story: A Case Study on the Reproductive System You are a columnist for a popular website that deals with women's health issues. Visitors to the site can submit their stories and questions through an "Ask the Expert" link on the site. In this scenario, a 26-year-old woman has posted her story and some questions regarding reproductive health. My name is Angela. I am a 26-year-old married woman with no children. My husband, Doug, and I have been trying to get pregnant for over two years now and my doctor has suggested that I consider fertility drug treatments. The irony of our situation is that I have been taking a birth control pill for five years to prevent getting pregnant, and now my doctor suggests that I take another drug to help me get pregnant. When I went off birth control, about a year ago, my menstrual cycle became very irregular. I had been taking a birth control drug called Ortho Tri-Cyclen. To be perfectly honest, I don't understand how it works because my periods were more regular when I was on the pill than when I went off of it. My doctor told me that the pill works because it tricks your body into thinking that it is pregnant. That just confused me even more. When I looked back on my decision to take birth control pills, I realized that I did not really understand how they work. I just do not want to make that mistake again. Before I consider taking any more drugs, I want to understand more about how they work. The drug we're looking into is called Clomid. I asked my doctor a bunch of questions, but I still feel confused. I looked up some stuff online when I got home. Here is some information that I learned from a website about how Ortho Tri-Cyclen works: Estrogen and progestin work in combination to suppress the hypothalamic-pituitary-gonadal (HPG) axis. This suppression leads to a decrease in the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. Maturation of the dominant follicle is inhibited under the decreasing levels of FSH and LH. Hormonal contraceptive use also leads to an increase in the viscosity of the cervical mucus, which inhibits sperm penetration and movement through the cervical canal. I am hoping that you would be able to help me understand how these drugs actually work.

Short Answer Questions 1. In my research, I found that the levels of "gonadotropins" in the body are critical to understanding how the drugs Clomid and Ortho Tri-Cyclen work. What are gonadotropins? What role do they play in fertility? 2. Some of the references talk about how "negative feedback" is involved in understanding how these drugs work. Can you explain what is meant by negative feedback? 3. My doctor told me that birth control pills contain small amounts of estrogen and progesterone, and these hormones prevent me from ovulating. I don't understand how giving me these hormones in a pill would prevent me from ovulating. I assume that it has something to do with the levels of the gonadotropins that I asked about earlier. Can you explain this to me? 4. In the information about Ortho Tri-Cyclen, it mentions that the hormones in the pill make cervical mucus thicker and stickier. Does this happen during my natural cycle? How are estrogen and progesterone involved in this process? 5. My doctor also explained that birth control pills "trick the body into thinking it is pregnant." She explained that women do not normally ovulate when they are pregnant. Can you explain to me why a pregnant woman does not ovulate? How is this related to how the birth control pill works? 6. My doctor explained that Clomid works by "tricking the brain into thinking that estrogen levels in the body are low." She explained that this is what leads to the extra stimulation of the ovaries to encourage eggs to be released. One of the references for Clomid said this happens because there is less negative feedback. Can you explain to me how this "trick" and the decreased negative feedback are related? Why would these factors lead to the stimulation of the ovaries? 7. My doctor told me that if I take Clomid, I would be taking it on days five through nine of my normal menstrual cycle. She explained that this is when it will have the greatest chance of stimulating the ovaries. What is going on during this part of the menstrual cycle that makes it the best time to take this drug? 8. I read an article that mentioned that women on Clomid may be more likely to get pregnant with twins, triplets, or more! The article said that normally there is a dominant follicle that releases a single egg, but Clomid can potentially make lots of follicles release an egg in a given month. How does Clomid do that?

Blood Everywhere: A Case Study in Blood An ambulance arrives at the scene of an automobile accident, having been summoned by an in-vehicle security system. What the emergency personnel find is like a scene from a horror film. Maggie Silvers, the apparent driver of the car, is sitting, slumped next to the vehicle, with blood covering her shirt and hands. Her car has clearly hit a tree: a branch is sticking into the driver's window, and the airbag has been deployed. Maggie looks dazed, and as the paramedics approach she says with a mixture of panic and relief, "There's blood everywhere!" Maggie is only semi-lucid as she babbles on about pushing out the broken glass in her car window. Maggie, a 48-year-old woman, is, indeed, bleeding profusely from multiple left-arm cuts and an especially deep laceration on her left upper arm. The paramedics stop the bleeding and move her quickly to the ambulance, after noting no other apparent injury. Her systolic blood pressure is 80 mm Hg (low), and her diastolic is not audible (too low to hear). Her heart rate is 122 bpm (very rapid), and her skin is pale and clammy, indicating peripheral vasoconstriction (narrowing of her blood vessels, particularly in the skin) and circulatory shock-like signs. On the way to the hospital, a paramedic begins transfusing normal saline solution (NSS; water with some NaCl, similar to body fluids, given directly into her vein). A fast hematocrit (HCT) test upon Maggie's arrival to the emergency department (ED) indicates that her HCT is low, but normal. Several vials of Maggie's blood are also sent to the lab for blood tests and typing. Two liters of NSS are transfused over the next hour while the ED physician sutures her deepest, left-upper-arm laceration. Despite no further bleeding since the paramedics treated her at the scene, Maggie's next HCT, tested one hour after the original HCT, drops to below normal. Aside from her present health problem, Maggie is otherwise healthy. She is admitted to the hospital for overnight observation.

Short Answer Questions 1. The "fast hematocrit" involves withdrawing a very small amount of blood via a finger prick into a thin capillary tube, spinning the sample in a centrifuge so that it separates into its components, and then measuring the components. In Maggie's case, the total blood volume in the capillary tube is 20 mm, the packed cell volume (red blood cells) is 7.1 mm, and the plasma portion measures 12.9 mm. Calculate Maggie's first hematocrit. 2. In the ED, blood is withdrawn from the vein and into a test tube. The packed cell volume (RBCs) is 1.45 ml, and the plasma volume is 3.55 ml. Calculate Maggie's hematocrit in the ED. 3. Explain why the HCT drops despite no further loss of blood. 4. Why do you think paramedics give normal saline solution (NSS) and not blood in the ambulance? 5. Why might a physician be reluctant to order a blood transfusion for Maggie, or for any patient for that matter, unless absolutely necessary? 6. Despite no blood transfusion, Maggie's hematocrit improves by the time she visits her physician for the removal of her sutures a week later. [See multiple choice question 3 for the calculation.] She is adequately hydrated. Explain the physiological mechanism for the improvement in her hematocrit. 7. Besides the HCT, what other component of blood could be measured to give a better understanding of oxygen-carrying capacity? Explain your answer. 8. Explain the relationship between Maggie's low blood pressure (when the paramedics first examine her) and her blood loss. How are her rapid heart rate and pale, clammy skin related to her low blood pressure?