a Fifth Chance Media book, ISBN 978-1-944861-02-5.
From the editor: Health care is nearly 20 percent of our GDP. The surest way to be a full participant in this massive and growing sector of the economy is to get an MD. But it is a substantial commitment for a young person to prepare for, enter, and complete medical school. What is it like day-to-day? To help young people (and old people advising young people) answer this question, I have placed a mole in one of America's medical schools. I'll be publishing his diary on a regular basis. Here's the first installment….
One week to go before entering medical school, Class of 2020, and I am two parts excited, one part anxious: excited about the first cadaver cut in Anatomy 101; anxious about aspiring to heal others, about having another trust me with vulnerabilities. How must I change to uphold the physician’s charge?
Why this book: (1) as a reminder of the enthusiasm with which this long process was entered, (2) in case it is helpful to students considering premed.
Personal background: With the exception of a few years overseas, I grew up in a wealthy American suburb with two well-educated parents and academically successful older siblings. After enjoying an uneventful K-12 in public school, I majored in biomedical engineering (GPA 3.8) at one of America's better universities, scored 37 on the MCATs, and could have started medical school shortly after graduation in 2015. I spent a year working, however, so that medicine would be an affirmative choice rather than a default. I enjoyed the engineering job, but now that I've seen the opportunity cost of not pursuing medicine I won't have second thoughts after paying tuition bills.
Anatomy begins at 7:00 am sharp. With the outside temperature well over 90 degrees Fahrenheit, we immediately know we are entering a different kind of learning experience kept at a chilling 55 degrees! Most of my classmates seem excited for a break from the 4-times a week, 2-3 hour morning lectures on cellular and molecular biology. Not only can these lectures be somewhat tedious, especially for the abundant biology majors, but everyone seems eager for something different from the traditional undergraduate lecture format. The class piles into the classroom and begins on time -- surgeons are punctual.
The trauma surgeon instructor briefly goes over dissection tool technique and we begin the exam of our “first patient”. Our first dissection focuses on understanding the role of the “superficial back muscles” on shoulder support and joint motion. The scapula, or shoulder blade, is an alien wing-like bone almost completely detached from the central skeletal system. Unlike most bones, the scapula is supported primarily by numerous muscle-tendon insertions with just a single bone-bone “pivot” at the lateral edge of the clavicle, or collarbone. The fine-tuned muscle contractions slide the scapulae along the back for precise positioning of the shoulder joint.
As I look around at my new classmates, scalpels in hand, most sluggish from a night of getting to know each other over booze and late-night burgers, you see a few patterns. Aspiring physicians include an abundance of type A personalities, which means that many clamor to be the primary dissector. However, once the dissection begins you can quickly see the few who are captivated by anatomical exploration through slicing and dicing. I would bet that those few pursue the cult of surgery, addicted to the “cut” as one of my surgical physician mentors put it.
Class ends at 12:30 pm and I grab lunch with my classmate who is a young father. It turns out that his wife is also starting a graduate program meaning their budding family is entirely supported by student loans. They're expecting a second child soon. He jokes that he’ll just use all his vomit-stained clothes for anatomy lab.
Class begins every weekday either at 7:00 or 8:00 am. Two days per week, classes, workshops, patient interviews, and other activities end before 1:00 pm. On the other three days activities conclude around 4:00 pm. We have anatomy lab once per week. The rest of the week is centered on lectures about cell and molecular biology, including signalling pathways, molecular structure-function pairings and cell microenvironment. Much of the material is familiar from my undergraduate biomedical engineering studies. However, after a year in the working world, I am surprised by how much I have forgotten. I spent a total of 6 hours doing work this week. Dinners were off-campus with classmates. A typical weekend activity is a pick-up soccer game, getting drinks downtown, or a class hike.
This week I learned about the National Board of Medical Examiners (NBME) Step I board exam. Typically taken after the second year of medical school, just before clinical rotations commence, the score on this exam is the most important criterion for the residency application (the first year of a residency is technically the future specialist's "internship"). There is some bad news for nervous parents who worried about getting a child into the right preschool to ensure entrance to the right elementary school to ensure entrance to a prestigious high school to ensure entrance to a selective college to ensure admission to medical school: the real career-determining educational institution is the residency.
Our dean gave us some additional bad news this week: there is a worsening shortage of residency positions. (See "Squeeze Looms for Doctors; More Medical Students Are In the Pipeline, but Too Few Residencies Await Them" (WSJ).) Medical students have responded to this situation by applying to 15-20 hospital residencies rather than the traditional 4-5. Residency admission committees have responded to this flood of applications by increasingly their reliance on Step I board scores. All of our tests for the first two years are in fact covering the same material as the Step I test.
In our morning cellular/molecular biology lecture series, doctors and researchers may preface a detailed explanation with "don't worry; you don't need to know all of this detail for the test." Nearly 20 percent of my classmates have at various points raised their hands to ask "is this going to be on The Test?" When the answer is "no," I wonder how many tune out the nitty gritty details of a cancer signaling pathway or the extracellular matrix remodeling in vasculogenesis.
Three days this week, including the weekend, I joined a group of 6 or 7 classmates at a local bar's happy hour for $2 beers and rail drinks. Roughly half of our class is female and one difference in conversation is that the men are less likely to talk about their romantic situation. Within the first 2-3 conversations with a woman, I've learned if she is single, dating, engaged, or married. About half of the women seem to be single, a fifth are engaged or married, and the rest are dating.
Though we have only recently met, it is already time for the class election. The positions up for grabs include president, vice-president, and a handful of Association of American Medical College student interest group representatives. Some eager beavers have been campaigning since the first week. There are three candidates for president and three for vice-president. All are male.
I did about six hours of homework total this week and went to bed every night before 11:00 pm.
Each week our class discusses a new patient that parallels the scientific theme(s) from lecture. Most medical schools are pushing away from the conventional medical school format: two years of basic science education followed by two years of clinical rotations in the hospital shadowing residents and attendings. The newer approach is integrating clinical experiences and lectures during the first two years.
This week we reviewed a patient with a metabolic muscle disorder who became addicted to pain medications and heroin. The case paralleled this week’s lecture topics of muscle structure, contraction and metabolism, including the dreaded Krebs cycle. A public health official came in to discuss the country's opioid epidemic. In 2014 the CDC recorded 28,647 deaths, triple the 2010 number, from opioid overdoses (prescriptions and heroin combined). We learned that "among new heroin users, three out of four report having abused prescription opioids prior to using heroin." (http://www.cdc.gov/drugoverdose/data/heroin.html) Most heroin comes from Mexico: “Researchers believe the border detection rate hovers around 1.5 percent — favorable odds for a smuggler.” (Washington Post). Mexican heroin is unlike the “black tar” Southeast Asian variety of the 1970’s. Mexican heroin is close to pure and frequently laced with potent fentanyl, a synthetic opioid over 100x as powerful as morphine manufactured in cartel labs. (Prince overdosed on fentanyl.) Overdoses rise when fentanyl is in the mix.
Week 3 went by fast because of a few firsts in anatomy. We continued dissection of the gluteal region and the posterior lower leg. I saw a nerve for the first time -- it was huge! The sciatic nerve runs through the thigh until it branches into the tibial and fibular nerve at the popliteal fossa (posterior knee joint). The sciatic nerve is about the diameter of a large pen with translucent threads firm to the tough running along its axis. This observation shattered the notion that nerves interact only at the microscopic level. I can imagine how hypertrophy or herniation of nearby muscles could constrict the sciatic nerve causing radiating pain down the leg. Interestingly, the tibial nerve lies superficial, above the arteries/veins, at the back of the knee. You do not want to cut yourself here… One of my teammates for our cadaver cut her hand with a scalpel, the fifth incident in three dissections. She was trying to isolate semitendinosus, a muscle of the hamstrings, with a scalpel and her hand instead of a probe.
Statistics for the week… Study: 8 hours (5 hours devoted to anatomy); Sleep: 6 hours/night; Fun: 4 nights out. Example fun: A fellow classmate (let's call her "Jane") and I joined the Hawaiian-shirted locals at the weekly outdoor swing-dance downtown. Dancing to the brass-heavy “beach music” band and wearing a thrift-store Hawaiian shirt, I would have fit in except for being 35 years younger than the average dancer.
In anatomy, we dissected the anterior thigh, lower leg and foot. Before this week, I did not realize there were two bones between the knee and ankle: the tibia and fibula. (To feel your fibula, locate the protrusion on the lateral side slightly below your knee and follow it down to a protrusion on the lateral side of the ankle.) One of the most interesting parts of this three-hour dissection was the opening of the knee capsule, which requires ripping through tough layers of ligament on both lateral and medial sides to arrive at the treasures: the anterior and posterior cruciate ligament (ACL, PCL, respectively). These are named for the criss-cross structure they form in the interior knee. Once we cut the ACL, a beautiful bundle of fibers from the anterior side of the tibia to the lateral condyle of the femur, it is amazing how much we could move the tibia in relation to the femur.
After the anatomy lab, orthopedic surgeons taught us how to conduct a lower leg exam. We learned to isolate specific axes of rotation to evaluate ligament integrity and range of motion. Tragically ironic, a classmate’s boyfriend injured his knee the next day. She conducted the exam and felt an increase in medial rotation of the knee and offered the diagnosis of a loose lateral collateral ligament. When asked what he should do, she responded, "I don’t know, ask me in three years. Your LCL is messed up."
Our patient case had type 2 diabetes, which includes two distinct phases. The first involves the desensitization of target cells to the action of insulin. Insulin acts as a “signal of construction” by stimulating target cells to uptake available energy and molecular building blocks such as blood glucose. As blood glucose remains high, pancreatic cells that secrete insulin become overworked and die. As pancreatic islet function is degraded, the patient transitions to the second phase, a severe, irreversible form of type 2 diabetes that mirrors type 1 diabetes. Importantly, patients who manage their diabetes before entering this second phase can reverse the entire disease. The lecturers, an internist and a PhD researcher, agreed that determining the mechanism of insulin resistance would win a Nobel prize.
One common drug class used to manage type 2 diabetes and to depress blood glucose is sulfonylureas. Sulfonylureas function by increasing beta-cell release of insulin. One of my classmates asked, "Isn’t treating type 2 diabetes with these drugs accelerating the degradation of beta cell function?" The internist responded "Yes, but sometimes we have to use them. When a patient’s glucose levels are off the chart, you have to use every option. Second, sulfonylureas are much cheaper than alternatives such as insulin injections. Many of my patients cannot afford anything else."
With exams in a month, a few classmates are already freaking out. We aren't being given the graded homework assignments to which they are accustomed and from which they could gauge their progress. We are supposed to determine what style of independent learning works for us. Instead of concentrating on learning, these classmates are worrying about exactly what is going to be on the Week 9 exam. Our drama for the week is that they apparently brought their uncertainty up with the Office of Student Affairs. I would have hoped that they'd have more faith in the system with which they are entrusting four years and more than $300,000 (tuition, room, and board).
Statistics for the week… Study: 8 hours (6 hours devoted to anatomy); Sleep: 6 hours/night; Fun: 4 nights out. Example fun: Friday night about 15 of us had a “jam session” dinner party. After spaghetti and homemade meatballs, we broke out the beer and instruments. The group included a classically trained cellist, two pianists who would have been welcome in most jazz clubs, and a harmonium(!) player. I was glad that I had brought my guitar, but I'm not sure that these real musicians were similarly glad.
Dissection investigated the shoulder joint. Our upper limb is similar to our lower limb in bone and joint structure. However, while most of our weight is translated through bone in our lower limbs, most upper limb weight is translated through muscles, the most fascinating of which is serratus anterior. This muscle originates on the front of the upper ribs, wraps around the body, under the shoulder blade, to insert on the anterior side of the medial border of the scapula (shoulder blade). This “boxer” muscle pulls the shoulder blade against the thorax ensuring it slides along the back when other muscles act upon it.
Lectures continued the discussion of metabolic processes, including the role of lysosomes, the recycling centers of the cell. Extracellular debris, and cellular parts are trafficked to these small vesicles to be degraded by powerful enzymes. Our patient case was Hunter’s disease, a lysosomal storage disorder caused by a mutation or deletion in a lysosomal enzymes’ genetic code. There are only about 500 Americans afflicted with Hunter’s, which affects nearly every organ system and can result in heart valve malformation, respiratory problems, liver/spleen enlargement and severe neurodegeneration. Individuals suffering from Hunter’s, which typically manifests by age 2, frequently cannot speak or comprehend basic stimuli. Life expectancy varies from 10-20 years.
A pediatric geneticist described treating Hunter's patients with Elaprase, a recombinant enzyme replacement therapy that replaces the mutated or absent lysosomal enzyme. This "orphan drug" costs over $300,000/year (see Forbes), but can't get through the blood-brain barrier to enter the nervous system and improve neural development. The geneticist explained that orphan drug prices are passed on to private insurance companies at an undisclosed negotiated price, paid in full by Medicaid without negotiation, or are paid for by the manufacturer when the patient has no insurance. Shire reported worldwide 2015 Elaprase sales of $552 million (press release).
We were done every day before 5:00 pm. I studied 1.5-2 hours after class each day in preparation for the exams that are three weeks away. There is a medical school test prep industry that includes phone-based flashcard systems such as Anki and Firecracker ($300 for two years). I haven't subscribed to any paid products yet because skimming through lecture slides and notes, then taking practice exam questions, is effective.
We got Labor Day off and our student affairs dean held a dinner party for those who stayed in town. We learned that for the past two years, approximately 20 percent of graduating students have gotten engaged to one another.
Statistics for the week… Study: 10-12 hours; Sleep: 6 hours/night; Fun: 3 nights out. Example fun: a Friday after-class soccer match followed by a BBQ with Jane’s family.
Two weeks before exams and the small library is packed in the evening. We have to review every topic since August while simultaneously being introduced to the complex biochemistry of the urea cycle, the process our body uses to eliminate ammonia freed from normal recycling and breakdown of protein and DNA. Free ammonia is normally turned into urea by the liver for excretion in urine.
Our patient this week was a 20-year-old woman suffering from a Urea Cycle Disorder (UCD) since birth. She had the cognitive function of a toddler. A few of my classmates were left speechless after seeing the patient and hearing from the mother about her round-the-clock caregiver role. She described struggling against the adult strength of her daughter during basic tasks such as bathing and feeding. UCDs are typically caused by a genetic mutation to an enzyme that catalyzes an intermediate product in the conversion from ammonia to urea. If not detected early, excess blood ammonia (hyperammonemia) can alter blood pH enough to cause irreversible effect on the nervous system or death. Most states' newborn screening programs now test for several UCDs. Treatment typically is a combination of strict dietary restrictions and nitrogen scavenger drugs.
We heard from a hospital Institutional Review Board (IRB) administrator in charge of approving clinical trial requests and access to patient data. The IRB does not evaluate the value of the proposed research; instead, the IRB evaluates if the project can be conducted in a reasonable manner to benefit and to protect the research participants. This process is historically a huge pain for physicians who want to conduct research. The board can take months to review a simple clinical trial proposal or data analysis project of patient data. She did not deny that the IRB process is cumbersome, but used the 1999 example of Jesse Gelsinger to explain why these protocols are followed. Gelsinger was a functioning teenager with a UCD that was so mild he should not have qualified for the trial to begin with. Scientists attempted to use adenovirus (influenza) modified with a functioning form of the mutated urea cycle enzyme to cure the patient. Potential dangers of the trial were not disclosed to the patient and his family. A principal investigator for this NIH trial had relationships with the pharmaceutical company providing the adenovirus vector. Gelsinger died from a massive immune response and liver failure. This tragedy triggered review of clinical trial procedures and halted many ongoing and future gene therapy trials.
After the 1.5-hour IRB presentation, an Emergency Room Physician talked about his experience with the IRB for a pain medication clinical trial. He clearly was frustrated with the IRB, but diplomatically limited his criticisms to "there is plenty of room for improvement."
Anatomy lab continued with the previous week's dissection of the shoulder joint from the anterior side. We saw the actions of the four rotator cuff muscles and observed the massive vessels and nerves near the clavicle. Between the clavicle and the joint capsule lies a fascinating mesh of nerve fibers called the brachial plexus, by far the most complex nervous feature we've seen so far. We learned how upper extremity range of motion is a function of three joints: sternoclavicular (SC), acromioclavicular (AC) and glenohumeral (shoulder blade-humerus). I never realized we have movement in the SC, the single point of contact between our upper extremity and our axial skeleton, when we raise or rotate an arm. When orthopedic surgeons came in to demonstrate shoulder exam techniques, nearly 20 percent of our young class had bad enough shoulders to line up for a free exam.
Statistics for the week… Study: 16 hours; Sleep: 6 hours/night; Fun: 2 nights out. Example Fun: Friday after-class soccer tradition followed by bowling night, in which we learned that one of our classmates is a former competitive bowler.
One week before exams; my classmates are nervous.
Lectures introduced the immune system, both the innate and the marvelous adaptive immune system. All of our immune cells start their lives as bone marrow stem cells. These stem cells undergo education, either in the thymus or bone, to ensure they do not attack healthy cells yet can potentially attack foreign antigens. I had always thought during an infection our adaptive immune system would create a new immune cell against this foreign structure. Instead, the diversity of potential antigens to which our body can respond is determined within the first few years of life by a process of "student" immune cells randomly self-mutating their antigen receptors (see VDJ recombination). Only about 1-2 percent of the total cells graduate from self-mutation school; the remainder kill themselves. The textbook says that our immune system ends up with roughly 1,000 billion cells that can recognize 10 million different antigens. When an unknown invader arrives, if it is among the 10 million antigens that we've prepared to fight since early childhood, we're in great shape. Otherwise we will need antibiotics or a trip to the hospital.
A doctor from the world's only hospital that does thymus transplantation came in. As mentioned above, the thymus is the schoolhouse of the immune system, educating immune cells to not attack self. Transplanting a donor thymus, typically obtained from a young child whose thymus got in the way of cardiac surgery, could theoretically eliminate the issue of organ transplant rejection. If a diabetic needed a new kidney, immunosuppressors would be used to destroy the patient's immune system and then the donor kidney and a donor-matched thymus would be transplanted. The regenerating immune system would be educated to not attack the patient nor the matched donor organ -- thymus education is additive! The challenge is to generate a comprehensive thymus donor database or even engineer a biosynthetic thymus.
We dissected the arm from the shoulder to the elbow joint. I was amazed by the vasculature (arteries and veins) as it branches from the major vessels in the thorax and the interweaving nerve structures (see brachial plexus). We saw the funny bone, a.k.a. the ulnar nerve, as it passes between the medial epicondyle of the humerus and the olecranon, or elbow bump, of the ulna. I also discovered my favorite joint: the radiohumeral joint with the annular ligament of the radius. The radial humeral joint allows rotation of the forearm (supination, palm up, and pronation, palm down). The radial head, a spherical protrusion at the proximal end of the radius, is encapsulated in a sheath that allows it to rotate around a fixed point. Listening to the PhD medical researchers who come in as lecturers, I am coming to appreciate the amazing opportunity of anatomy lab. The researchers are experts on test tube experiments, but haven't had time to look at the circulatory system or liver anatomy, for example.
Statistics for the week… Study: 18 hours; Sleep: 6 hours/night; Fun: 2 nights out. Example Fun: Friday after-class soccer followed by a repeat of the Week 4 jam session. More than half the class showed up and most of them sang along, despite any lack of formal musical training.
Exams begin next week. Type-A Anita is particularly nervous. Beginning last week she has refused to learn anything that is more in-depth than the NBME questions: "only high-yield." She interrupts class once per day to complain when a professor gives more detail than the Step 1 exam books do. She also requests clarification about the number of questions per exam topic. She dropped her sweet Midwestern demeanor and submitted a formal complaint to the administration when an older physician said males have to work more to learn patient interviewing because women are more naturally caring.
Lectures focused on glycolysis and summarizing metabolic pathways. A rather plump gastroenterologist in his 50s gave an "energy" synopsis about different states of metabolism. These lectures were paired with our patient case, a young anorexic teenager. Anorexia fits with the metabolism unit because it forces the body to break down protein to use for gluconeogenesis. We heard from her doctor that the patient is on antidepressants and receiving psychotherapy, but didn't get to meet the patient.
We finished dissecting the upper extremity with the elbow, forearm and the bewildering hand, whose muscles and vessels entail hours of dissection. I share my cadaver with three other students. Yet, with three hours of dissection time, we had explored only about 10 percent of the hand. Fortunately, the instructors convinced a chief surgery resident to spend his evenings dissecting a demo cadaver and then come in at 10:00 am to give us a guided tour of a perfectly dissected hand. We were doubly appreciative of his efforts after we heard about his 24-hour hospital shifts.
One of our most passionate and funny doctors spoke about using ultrasound to investigate the shoulder and upper arm. Ultrasound sends high frequency sound waves into the body and relies on differences in the ways that tissues reflect or absorb the sound. We broke up into groups of six, each provided with a donated battery-powered 10 lb. ultrasound machine. The expert (attending) arrived at each workstation to help us diagnose each other. We were able to see torn muscles, ligament damage, tendinitis, and bursitis. As with Week 6, a high percentage of our classmates were able to supply examples of musculoskeletal damage. I contributed a torn supraspinatous (rotator cuff) muscle torn in the college weight room.
In an after-workshop discussion, our professor described his frustration that the medical school accrediting body, Liaison Committee on Medical Education (LCME), limits the number of "formal instruction" hours. "I'm not exactly sure, but it is only about 25 hours per week," he said. He recounted stories from his professors' education in the 1920s. For example, a instructor asked a first year class if anyone was uncircumcised. Two students raised their hands. They were instructed to drop their trousers, and in the pursuit of education, were circumcised in front of the entire class, including the two female students. His own 1950s education did not include any in-class circumcisions, but they were at school for 12 hours each day, with some mandatory Saturday sessions. Anatomy lab dissection was 4 hours per day compared to our 4 hours per week. Our professor noted that passing the NBME exams requires more knowledge than for comparable tests in years past. Thus today's medical student faces greater pressure to study independently.
Statistics for the week… Study: 35 hours (about 5 hours after class each weekday plus more on the Sunday); Sleep: 7 hours/night; Fun: 1 hiking excursion with Jane.
We have four straight days of exams, covering clinical exam skills, biochemistry, anatomy and cellular biology. Exams begin at 8:00 am, but on two days we were finished by noon. Our first, and main exam is a practice NBME Step 1 using prior, retired questions. The biochemistry and metabolism questions are quite similar to the MCAT. A classmate sent a message our GroupMe after he finished the exam: "There goes my Derm practice out the door." Anita, and some of the other more sensitive, nervous individuals, did not find this funny. (Dermatology, along with orthopedics and surgery, are some of the most competitive residencies, requiring high Step 1 scores to get matched.)
Anatomy was a sore subject for many. The exam required detailed knowledge of discrete muscle group innervations. There was grumbling afterwards: "I couldn't read the poor quality images"; "Who cares what the fascial layer is called?" I am grateful our medical school still purchases cadavers for us to learn anatomy; numerous schools are replacing cadavers with electronic images for anatomy education. There is no substitute for the real thing.
After our last exam, we were invited to a cocktail party by a wealthy local sponsor of the medical school. It was pouring rain, but they had a valet service working in their front yard--I'm not sure it was a big night for valet tips given the medical students' typical debt load. The mayor and board members of the local health system were there to welcome our class to the city. The city symphony director played a few original jazz compositions on the piano. The class stayed late drinking martinis at the open bar and smoking free cigars.
I learned about tension among some physicians who teach us. Most of them love it. However, some are frustrated by the pressure from the health system to teach yet still are expected to have the same patient load. Instead of spending less time with their overbooked patients, they usually just stay later.
The celebration continued at our classmate's apartment complex. Our whole class was there, including the few married couples. The diversity of ages and lifestyles was illustrated by someone doing the college-favorite "slap the bag" of disgusting Franzia wine next to the 27-year-old father of two.
Statistics for the week… Study: 35 hours; Sleep: 7 hours/night (more than previous weeks due to going to bed earlier); Fun: 1 night out at cocktail party after exams.
With the first exams finished, we are all more comfortable with our roles as medical students. My comfort level rose to the point that I ordered a stethoscope. I'll be ready for next week's "white coat" ceremony.
Anatomy this block will focus on the cardiopulmonary system. In preparation for removing the chest wall, we dissected the anterior neck. The carotid artery was huge, about the size of an adult's thumb, and we could see the plaque that had built up during 97 years of living prior to becoming a cadaver. We got a beautiful view of where the common carotid artery bifurcates, forming an important structure called the carotid sinus. The carotid sinus contains nerves with specialized pressure sensors that regulate systemic blood pressure. A few decades ago, doctors investigating hypertension or shortness of breath would palpate and briefly constrict the carotid sinus to ensure blood pressure changes occurred. However, this can cause strokes from plaque rupture and we learned that therefore the practice has been discontinued, but we haven't yet learned about modern diagnostics.
Lectures focused on embryology with a patient case of fetal alcohol syndrome. So many coordinated events occur within the first two weeks post-fertilization, it is remarkable how rare serious birth defects are. One fascinating process is how the embryo creates a left-right axis. A region of cells have a single cilium, a vibrating thread similar to the flagellum that propels sperm cells. Coordinated beating of these cilia produces a net leftward current and creates a concentration gradient of signaling molecules to turn on "lefty" genes. We learned about sinus invertis, in which the body is flipped left-right. The condition affects roughly 1 in 10,000 individuals, many of whom have no symptoms at all! We also learned about some more serious cases of birth defects, e.g., sirenomelia ("mermaid syndrome") where the lower extremities are connected, and encephalocele, where the skull does not fuse correctly and the brain grows outside the skull.
Our patient case involved a teenager whose biological mother had used alcohol, cigarettes, marijuana, and cocaine while pregnant. "Greg" was born with fetal alcohol syndrome and addicted to cocaine. State social services agencies automatically investigate every case of fetal alcohol syndrome and, in this case, Greg was turned over to a foster mother, who was the primary speaker to our class. The foster mother, who quickly became the adoptive mother, told the story of how she came to love this child and the role of her Christian faith in the process. There was a lot of crying and the still-unanswered question of how the biological mother could have done this to Greg. Much to everyone's later-expressed surprise, when Greg finally walked into the room he was articulate, though nervous, with none of the aggression common to patients with a history of fetal alcohol syndrome. Greg was aware of his history and challenges. He described being frustrated by his poor memory and difficulty learning abstract subjects such as mathematics. However, he enjoyed history and socializing with other students at his special-needs school. We were impressed by Greg's determination and perseverance, but It seemed likely that he would require lifetime assistance from a responsible adult.
The case sparked a lively discussion on the legal ramifications of drug abuse while pregnant, a matter governed on a state-by-state basis. The spectrum of laws ranges from criminal prosecution if a child is born addicted to drugs or showing signs of fetal alcohol syndrome to no consequences beyond the potential for losing custody of the baby. Some midwestern states are in the middle of this spectrum, with a rehabilitation mandate for pregnant women who consciously abuse drugs and alcohol. Greg's physician opined that the potential for criminal prosecution was counterproductive because it dissuades addicted mothers from continuing with prenatal care. Women who'd previously articulated feminist positions in the classroom immediately voiced their objections to sanctions against mothers on the grounds that this was a step on a slippery slope toward infringing on a woman's abortion rights.
Later in the week, three primary care physicians led a discussion on how to approach patients about medications and drug usage. Doc 1 opened with a story about taking her 12-year-old daughter to a specialist. The nurse stared at the computer screen and read the questionnaire out loud without looking at the 12-year-old patient and mother seated nearby. "Do you drink?", "Do you smoke?", "Do you use illegal drugs?", "Do you feel safe at home?" This tale of attempted human interaction in the age of electronic medical records prompted Doc 2 to chime in: "Never trust the medication list in Epic ['MedRec'] as it is rarely up-to-date, and will certainly not include more sensitive drugs and behaviors." Doc 3 seems to be a contributor to this phenomenon, saying that he is cautious about adding to a permanent electronic record that is accessible to the patient on request. "I never put a 'suspected heroin use' note in the chart," he said, "I just keep a note on my desk."
Doc 1 told us to remember that it is not just illegal drugs that are used illegally. She had prescribed a muscle relaxer and prescription-strength ibuprofen (NSAID) for a patient with a back injury. After three months, the patient said that she'd stopped taking the medications because her middle school daughter had been pressured into stealing them by her classmates. When the daughter began to refuse, her "friends" threatened the mother that they would "jump the house" (?) to steal them. Despite the limited potential for getting buzzed off a muscle relaxer, Docs 2 and 3 were not surprised. Lesson learned: lock the medicine cabinet.
Statistics for the week… Study: 10 hours (1-2 hours after class each day). It has been easier to study this block's organ systems instead of the abstract biochemistry pathways that we were learning in the last block. Sleep: 6 hours/night; Fun: 2 outings. Example fun: drinks and music at Thursday downtown rooftop party and a class happy hour at a local pub.
We started our exploration of the respiratory system in anatomy by using bone saws to remove the chest plate, thus opening the thoracic cavity. Half an hour after we started sawing, I was holding a human lung: heavy, fluffy, yet slippery to the touch. Unlike textbook depictions, they are asymmetric. The three-lobed right lung is larger while the the left lung has only two lobes. The aortic arch and descending aorta carve out a large groove in the posterior left lung. Comparing cadavers, it wasn't hard to spot a smoker's lung: copious amounts of black specs on the exterior plus one cadaver had burst alveoli. If you see a doctor smoking you'll know that he or she really loves cigarettes.
My group finished early and snuck a peek by opening up the pericardium (membrane that covers the heart). The heart is surprisingly small, about the size of a clenched fist. We don't have any information about how our cadaver donor died (aged 97), but we noticed a dark red spot on the left side of the heart, surrounded by firm white tissue. Our instructor explained that this indicated a left ventricular myocardial infarction ("heart attack") and said that, if the patient had survived, the affected area would have remodeled into tough scar tissue. One small spec on a small organ is the difference between life and death.
We learned in lecture that the breathing system is like two springs: (1) the lung, which wants to collapse, and (2) the chest wall, which wants to expand. The lungs are stretchy, with a third of the elasticity from the tissue itself, and two-thirds from surface tension of the copious fluid coating the airways. They're constantly being pulled open by the pleural membranes, connected to the chest wall. We disrupted the balance when we cut through a rib, which sprung outward, no longer constrained by the recoiling lung.
Our patient for the week had been morbidly obese, which led to sleep apnea, which led to pulmonary hypertension. Excess weight on her chest and neck obstructed airways and elevated thoracic pressure. Prescribed a CPAP oxygen machine, her compliance was haphazard, which is typical with this immensely uncomfortable contraption, despite the patient's ability to choose her favorite mask color. Sleep apnea, with its intermittent decreased blood oxygen saturation, can lead to increased pulmonary artery pressure. This had caused her right heart to work harder pumping deoxygenated blood into her pulmonary arteries. Over the years this made it impossible for her to exercise. She felt continuously exhausted, unable to walk up a few stairs or stay awake during any prolonged meeting. She quickly used up all her vacation and sick days and had to quit her job, moving in with her sister 200 miles away. Her new doctor recommended she speak with a pulmonary hypertension (PH) specialist, a relatively new field spurred on by the rise of obesity and sleep apnea. The PH Doc described his reaction after the first visit: "I did not expect her to live for more than two-years. I thought her right heart would fail." He continued by explaining the unfortunate truth for PH. "Pulmonary hypertension was an inescapable death sentence until the late 1990s. There is no surgical intervention and no drugs. Studies showed that over 50 percent of patients with severe PH die within two and a half years." In the late 90s, pharmaceutical companies developed new classes of drugs to treat left heart failure and hypertension. Some of these turned out to temporarily reduce pulmonary hypertension, giving patients a brief window in which to lose weight. Our patient was able to complete an aggressive exercise and rehabilitation routine. Five years post-diagnosis, she is no longer morbidly obese, exercises daily, and has gone back to work part-time.
The PH Doc ended by reminding us not to be blinded by obesity in a patient: "Doctors too often blame all symptoms on obesity, even if there are other pathologies that can be treated." For color he told us about the challenge of not offending a patient while saying "we need to send you to the zoo where there is a larger-sized scanner…"
Sunday evening a few students were invited to my favorite professor's cabin. She is a never-married woman in her late 60s who has dedicated her life to the craft of trauma surgery. She entered medicine expecting to go into family practice. While a third year student, she requested to be sent for her family medicine rotation to a rural area. She drove into the mountains to a small mining town of 10,000 with two family physicians. Although regretting her decision at first, it was here that she learned to love emergency medicine. Sitting around the bonfire, she shared vivid memories of driving the ambulance up moonlit dirt roads to a mine and going down the shaft to retrieve injured miners.
What has changed in trauma surgery? "Well the cases have changed," she answered. "I started out treating young males in high-velocity, multi-trauma injury cases: car accidents, gunshot wounds, stabbings. Now it is mostly low-velocity cases: an elderly patient who has fallen. The family feels terrible for not having been there when the trauma occurred. The family flies cross-country to say 'Do everything you can to keep Grandpa alive,' not understanding what this requires doctors to do. Too often they ignore palliative care." She'd learned about hospital funding priorities: "It is easy to find donors for a state-of-the-art pediatrics wing; there is no money to remodel a decrepit geriatrics ward." Her bonfire advice to us: (1) find a field where you will get more interested in it as you go on; (2) you can be happy in more than one residency field (i.e., don't cry if you don't get your first choice).
Statistics for the week… Study: 8 hours. Sleep: 6 hours/night; Fun: 2 outings. Example fun: Camping with Jane and Sunday BBQ at trauma surgeon's cabin.
This week: White Coat ceremony; an exciting heart dissection lab; and our first real patient interactions.
In anatomy lab our goal was simple: remove the heart. Most textbooks depict the heart as a vertical organ, with the left and right atria lying on top of the muscular left and right ventricles. Our trauma surgeon described this as one of the greatest illusions of human anatomy. Instead, the ventricles are anterior to (in front of) the atria. We began by opening the pericardium, revealing the great vessels leaving and entering the heart. The aortic arch got several "oooh's and aww's" as we constricted this massive 1-2-inch-diameter thick-walled vessel. Once all the great vessels connecting the heart to the body were cut, the student would run around holding a human heart in the air, like Simba was held up in the Lion King.
Lectures detailed the embryological development of the lungs. Lungs begin developing at around 20 weeks gestation (18 weeks after fertilization; gestation is measured from the last menstruation). However, due to a lack of sufficient gas exchange sacs to sustain respiration, the lungs do not become pre-viable (sustainable out of the womb) until 23-24 weeks. Even after 24 weeks, a baby's lungs are barely developed, and the most common cause of death is respiratory distress. The slightest complication, for example, a respiratory infection, could lead to death.
Our patient case was a baby born at 24 weeks, about 16 weeks before she should have been born. The mother detailed how she was having a healthy first pregnancy when she suddenly went into a rare form of premature labor. An emergency C-section saved the baby and herself. "Kate" was brought into the world at 1 pound, 6 ounces (normal baby weight is 6-8 pounds).
The family expressed pure love for the neonatologist who "gave life to" Kate in the Neonatal Intensive Care Unit (NICU). "You should all become neonatologists," exclaimed the mother, "and if not neonatologists, then obstetricians!" The young couple had thought that the birth was the difficult part, but at 26 weeks Kate had a severe hemorrhage in the developing pulmonary vessels. As the neonatologist and nurses scrambled around the incubator, the parents were stunned. The neonatologist absently muttered, "This is not good." As the mother recited this trauma, she paused and broke out in tears. The father continued, "We did not know what was happening. One moment it was fine, the next, lights were blinking everywhere, sounds going off, people running." Blood vessels in the lung had ruptured. There were two serious concerns: first, the ventilator, which is breathing for the baby, gets clogged. The neonatologist and nurses frantically tried to vacuum blood out of the airways to prepare to insert another plastic trachea tube to ensure the airways remain open for respiration. After this was successful, the neonatologist knew the longer-term threat: stopping a massive bleed causes a sudden large volume return to the heart. When the heart pushes this additional blood into systemic circulation, immature blood vessels in the brain can rupture. If the baby does not die, this causes severe brain damage roughly half the time.
The neonatologist and family spent a nervous night waiting for to know if this cerebral hemorrhage had occurred. The family described their euphoria when the smiling and crying neonatologist came into the room with the test results: the blood vessels of the brain did not leak. The whole class crowded around as the family showed pictures of Kate today: a healthy, albeit slightly small, energetic toddler.
The White Coat Ceremony is a tradition dating back to 1993. Friends and family descend on the medical school to watch deans help each student into a white coat. The 1.5-hour ceremony was followed by a reception where parents snapped away with smartphones. The next day I would wear my white coat with my first patients, shadowing a Primary Care Provider who had trained in the Navy, but left after his four-year service obligation.
After the nurse took vitals, I introduced myself as a student, giving each patient the opportunity to demand a fully trained doctor (nobody did!). Then I interviewed the patient and performed any exams I felt pertinent, such as listening to the heart and lungs. I then reported back to the physician and we would return to the room together for discussion with the patient. It was empowering to walk into the patient room with my white coat on and a stethoscope around my neck!
Our first patient's chart indicated an alcoholic smoker with Chronic Obstructive Pulmonary Disease (COPD). An episode of pneumonia had put him in the hospital for a week and he was here for a follow-up to confirm that his lung tissue had recovered. The lungs looked as good as they were going to get, so we sent him home. Next we treated a child's ear infection, saw a type 2 diabetic, and checked on a hypertensive patient. Our last patient, in his mid-20s, had knee surgery nine months previously and was prescribed oxycodone for post-operative pain. He had been transitioned to tramadol, a less intense opioid, and, after reviewing the chart, the physician and I agreed he was likely asking for a refill, which should be denied. I asked if I should remain outside. My attending said, "No, you should see this. As a doctor you'll deal with it too much." After a brief exam of the knee, the conversation quickly turned to the subject of getting a tramadol refill. The doctor said that it is time to transition to a different pain-management strategy. The patient asked, aggressively, "Why? This is working. It's the only thing that helps with the pain. How could you do this to me?" When the physician would not budge, he put his hands over his head in desperation.
The four-hour clinic taught me to make sure to get the full list of prescription drugs each patient is on. We had to consider four drug interactions when evaluating a switch to a new hypertension pill for our patient with high blood pressure, who was already on 12 different medications. None of my classmates were surprised by this story; one shadowing a neurologist said, "Two of my patients were on over 17 drugs."
Statistics for the week… Study: 14 hours. Sleep: 6 hours/night; Fun: 1 outings, class halloween party! Medical school budgets bring out homemade costumes. My favorite was Ron Burgundy and Veronica Corningstone of Anchorman.
We finished respiratory physiology with a lecture on arterial blood gases. Breathing allows the infusion of oxygen into the bloodstream and the removal of carbon dioxide produced by cellular metabolism. The respiratory rate is normally regulated by the amount of carbon dioxide in the blood, not by the amount of oxygen. CO2 is tightly regulated because carbon dioxide determines the pH of the blood. Remember that soda contains carbonic acid. When the can is cracked, carbonic acid is converted into CO2 and water, i.e., fizzy water. The reverse process, of CO2 in the blood turning into carbonic acid, results in acidic blood. The body tries to maintain a slightly basic blood pH of 7.4.
My favorite trauma surgeon used some of her patient experiences as case studies to describe the different permutations of arterial blood gas states. In one example, a drunk 18-year old falls three-stories. He is found unconscious, not breathing, with O2 saturation (sat) levels severely depressed at 60%, and CO2 levels severely elevated. The patient is suffering from respiratory acidosis. As the patient is transported to the hospital in an ambulance, his O2 sat rises to 80%, but CO2 has dropped below normal. The high-school-age EMT raised the patient's oxygen saturation levels with the breathing bag, but was squeezing it too quickly, causing increased expiration of CO2 and respiratory alkalosis.
The patient case was "John," a 40-year old male suffering from life-threatening asthma since the age of four. Growing up, his condition was successfully managed by the family pediatrician. John's father was a teacher and John emphasized how this doctor had tailored the treatment and medications to his family's modest budget, e.g., by finding low-cost alternative medications and free samples. In college, the asthma spiraled out of control. "I saw a PCP [primary care provider] at college once. The guy immediately insulted my pediatrician saying the way I was managing my asthma was terrible." The PCP scoffed when John said the treatments were working well for him. John never went back and lost touch with the medical system. As his uncontrolled asthma began to worsen (John now admits the college PCP might have been right), he used home remedies. When he was having an asthma attack at night, he would brew a large pot of coffee and sit outside on the porch in the middle of the freezing night drinking cups of coffee with his plump pug (caffeine would relax his bronchioles). "I probably should have gone to the ED many times," John said, "but I would push the limits. Also, I knew how much it would cost me so I gulped that coffee."
John's asthma said that his asthma improved after he "moved and started a new job," enabling him to see the pulmonologist sitting next to him. It turned out that the "new job" was a cardiology fellowship and the pulmonologist was his attending. She joked that her fellow/patient was non-compliant and John admitted that it was difficult to find time to take care of himself. He sees patients as part of the fellowship, has two toddlers at home, and moonlights at the VA to support his family (a fellow earns about $60,000 per year). John noted some additional financial pressure from a recent regulation requiring eliminating Ozone-depleting chlorofluorocarbons from the inhalers' ejection mechanism. Although the drug itself was the same, this slight tweak to the mechanism allowed pharmaceutical companies to re-patent medications that formerly had generic competition. Prices soared from single digits to hundreds of dollars per inhaler. John said his insurance now covers most of it, but many patients have to pay out-of-pocket due to high deductibles. John noted that for some patients the inhalers can cost more than their mortgage payment, leading to abandonment of the optimal medications. John emphasized the need to listen to patients: "If they say something is working, don't brush it aside like the college PCP."
Anatomy lab was incredible, by far the most fascinating day thus far in medical school. After an early morning excursion with Jane to pick up pastries at our favorite breakfast place, we entered the cadaver lab where a fresh pig's heart from the local butcher awaited each student. The human hearts we removed last week were preserved for a later date once we can appreciate pathological conditions. We were quite timid at first. The surgeons and cardiologists went over and gave us a little instruction about where to make the first scalpel stroke, then said "just enjoy exploring wherever your heart desires." As soon as we opened the hearts, which we're told are almost identical to a human's, we saw an unfamiliar environment. Tendinous fibers, also known as heart strings, criss-crossed in the ventricular chambers connecting the atrioventricular valves to papillary muscles on the heart chamber wall. We rubbed the translucent leaflets of the heart valves in between our fingers. I saw and felt the beautiful tree-like muscular protrusions of the ventricular wall that help guide the flow to their destination, shattering my vision of the interior heart as a smooth surface.
Afterwards my favorite trauma surgeon gave a lecture on the aging heart. She described how the current generation of physicians were all trained on a younger population. Now, when physicians apply this standard of "normal" to older patients, many normal aging processes are diagnosed as pathological. For example, during aging the whole long axis of the heart begins to shorten. This is often misconstrued and overdiagnosed as a pathological state. She cautioned, "Get used to this. You are going to be dealing with an older population."
Last week's ear infection patient and I now share something: fleas. I have decamped to Jane's house until the fumigators can come. The physician with whom I saw the toddler calmly said, "It happens sometimes. Downside of seeing kids."
Statistics for the week… Study: 12 hours. Sleep: 7 hours/night, fleas kept me up one night; Fun: no downtown outings. Example fun: movie night with Jane bedtime 9:00 pm.
"I thought I was in a nightmare," one classmate wailed the day after election day. Every classmate seems to have voted, but none openly support Donald Trump. Type-A Anita held a class election party at her apartment with "I'm with Her" plastered on every wall. One classmate commented about the ease of registering to vote in a new state. He used an out-of-state ID as proof of identity but never had to show any proof of residence: "I just typed my address into the online voter portal. They never requested a utility bill, or anything. The bouncer at Friday's bar looked at my ID more closely than the election volunteer." Jane and I left before the results were in, but the mood of our hostess gradually darkened.
On post-election Wednesday, our class president sent a GroupMe message to the class: "If anyone would like to talk about last night's election, please reach out to myself or the VP." I stopped to join a conversation among three students in the hall. A proudly gay student said, "I always believed most people thought like me. I feel so alone. I don't feel safe. I never realized how many racists there are in America." I asked him what he thought about Peter Thiel's speech at the RNC? He had never heard of Peter Thiel. A rural West Virginian said that her entire family supports Trump, but she cannot. She described half of American voters as "brainwashed over guns," but said she still loves her family.
At our monthly journal club, where an instructor leads a six-person discussion of an academic paper, a student asked to be excused to make a phone call. The female biophysicist replied, "Well, apparently, anything goes now. Why not? Go ahead." I chuckled, but Anita began to cry and excused herself.
Anatomy lab was not as exciting as last week: a short dissection, mostly identifying different structures that had not yet been removed from the thoracic cavity. We observed the descending aorta as it passes through the diaphragm into the abdominal cavity. One cadaver had an enlarged aorta, many had plaque build-ups. We observed the venous drainage system including the azygos and hemiazygos veins that drain the thoracic wall. We compared this system among cadavers and noticed the immense amount of normal variation. Some cadavers have the hemiazygos system drain the entire left thorax into the azygos vein, a tributary to superior vena cava. Another variant had divided drainage basins with some going to the azygos system and some draining into the left subclavian vein. One cadaver had a visibly enlarged azygous vein. The trauma surgeon immediately started looking for deep venous thrombosis (DVT). If a large vein in the leg is occluded, the azygos vein acts as collateral circulation, partially bypassing the blockage. We could not find any blockage.
We also observed the paravertebral ganglia column, a fascinating bunch of neurons that run on either side of the vertebrae. These sympathetic nerves have their cell body, e.g., nucleus, in the spinal cord but their axon exits the vertebrae and runs parallel alongside the vertebral column. It was small and easily mistaken for connective tissue. An instructor complimented our group for identifying this nerve!
Lectures featured a pediatric cardiologist. The whole class quickly fell in love with her three decades of stories about saving babies with congenital heart defects. Congenital heart defects, such as atrial septal defects (ASD), ventricular septal defects (VSD) and patent ductus arteriosus (PDA), are not uncommon. She explained these in the context of embryological heart development. Fetal circulation is quite different than after a child's first breath. The fetus uses hemoglobin with a higher oxygen affinity to steal oxygen bound to the mother's hemoglobin.
Most fetal blood bypasses the pulmonary circulation of the lung through the ductus arteriosus, a shunt between the pulmonary artery and aorta. The ductus arteriosus typically closes within a few hours to days after a baby's first breath. However, if the ductus arteriosus fails to close, the PDA could lead to severe hypoxia, heart development problems and death. Cardiothoracic surgeons can now close this using a catheter guidewire system instead of open heart surgery. Frequently the PDA patient has other heart defects that require more invasive surgery. Babies with an ASD, VSD, or PDA can live completely normal lives once this is fixed. She concluded by showing the class pictures of her "extended family".
The patient case followed the story of a baby with an exceedingly rare genetic disorder. Based on an ultrasound, physicians determined that "Kate" would never be able to talk, and would suffer from severe neurological impairment. Only fifty percent of babies with this disorder do not make it to birth, and a mere five percent make it to one year of age. Physicians advised her parents to terminate the pregnancy. The parents refused, "She deserved a fighting chance. Her fight was between herself and Him (pointing up to the sky)."
An early C-section saved Kate and the mother. Kate was then whisked off to the infant operating room to begin work on her full range of birth defects. These would include several life-threatening heart defects, respiratory distress and terrible GI troubles. She was placed on extracorporeal membrane oxygenation (ECMO) which functions as the baby's lungs and heart. The father broke down when he recounted his memory of this machine. Each ECMO machine has a lever attached. In the event the power goes out at the hospital, he would have to crank the lever to continue pumping oxygenated blood into Kate.
Now seven years old, Kate is fed using a G-tube and is unable to speak words. However, she can smile, laugh, and walk with assistance. Kate enjoys playing with her two younger, but already bigger, siblings. Medicaid pays for a daily caretaker to assist the parents. One classmate asked, "What are your hopes for Kate." The parents responded, "Kate has surpassed everything we hoped for. We were told she wouldn't survive the pregnancy. She did. We were told she wouldn't survive past the age of one. Every additional day is a blessing."
Statistics for the week… Study: 15 hours. Sleep: 7 hours/night, still staying at Jane's; Fun: 1 outings. Example fun: Dinner party with Jane's family.
Sonographers and clinicians demonstrated echocardiography. The ultrasound radiologist said, "This will be the moment everyone is captivated by ultrasound." She was not wrong as we gazed at our hearts in action. Echos are a fantastic way to noninvasively get a snapshot of the heart. My classmates loved using the "color doppler" feature to visualize the blood flow in and out of the different heart chambers. Due to Doppler effect, blood flowing towards the transducer compresses the sound waves and thus reflects sound at a higher frequency; blood flowing away from the transducer stretches the sound waves and thus reflects at a lower frequency.
Lectures continued on cardiac output and numerous regulatory mechanisms of the cardiovascular system. Cardiac output is governed by metabolic demands of the body. I was fascinated by the principle of "peripheral vessel capacitance". Arterioles (small arteries) conduct rather than store blood. Arteriole smooth muscle tone determines the resistance of these rigid tubes by changing the diameter. Venules (small veins) are slack by comparison due to high levels of elastic fibers and the low amount of smooth muscle in their walls. Arterioles and venules behave as a combination of resistors and capacitors for blood. Venules collectively are a massive reservoir of blood. A sudden increase in cardiac output and increased blood pressure can be handled by charging the venule reservoir rather than by returning venous blood to the heart. In the event of a hemorrhage, the vessels will discharge to maintain arterial blood pressure. Smooth muscle contraction of the arteries increases resistance and thus decreases flow, whereas smooth muscle contraction of the venous system leads to a decrease in capacitance and increased flow. It seems to me most blood pressure research and pharmacological intervention is focused on manipulating arterial muscle tone. I wonder how venous tone may be dysregulated in pathologies such as hypertension? (see "How changes in venous capacitance modulate cardiac output", Tyberg 2002)
The patient case involved a late-50s male who suffered a heart attack. "Jack" was also a type 1 diabetic diagnosed at an early age. He lost his financial industry job in 2009, along with his insurance, then had a heart attack a month later. During his week in the hospital, physicians put him into a medically-induced coma, which the patient said saved his brain function (because an awake brain would place a greater demand on the injured heart?). He recovered well and is back to work in a "less-stressful" job. The enormous bill was paid in full by a charitable organization associated with the hospital.
Due to his chronic condition, type 1 diabetes, he deals with nearly a dozen specialists, including an internist, rheumatologist, cardiologist and endocrinologist. He prioritises his cardiologist's' recommendation over treating his joint pain from type 1 diabetes after his rhematologist recommended he switch to a drug which his cardiologist vehemently opposed putting him on. Jack complains that he does not know how his heart is doing now. He lives with perpetual uncertainty. He knows he should lose 15-20 pounds. The cardiologist said the tests that might shed light on the heart's condition are not economically justified. When Jack mentioned his concern, the cardiologist said, "the question for patients after the first heart attack is not if, it is when, the next heart attack will be."
A quirky neurosurgeon presented his research interests to the class. He opened with, "Fracking will save neurosurgery!" He explained that neurosurgery involves an astronomically expensive procedure that, even when successful, frequently results in disabled individuals who cannot support themselves. "If a bomb went off at the neurosurgery conference, public health would not be affected. Only rich economies can support such a field." His research dream is to find a neurosurgery procedure that has an actual economic benefit. This lecture was a good reminder that a country's GDP is not a great measure of a country's wealth; if everyone gets diabetes the GDP will go up from increased health care spending, but the average American will certainly not be better off.
Next, an ENT specialist described her interest in hearing loss. The ear is a masterful mechanical device that focuses sound waves and transmits it to a circular fluid drum called the cochlea. Sound energy hitting the ear vibrates the fluid inside the cochlea. Specialized nerve cells innervate the cochlea bearing tiny hair projections into the fluid that deform at pre-set frequencies. These nerve cells send this signal this information to create the sense of sound. Medicine now has the ability to implant artificial cochleas. Our ENT lecturer was trying to determine at what age these prosthetics should be implanted to get the best hearing outcome. She presented a case in which one sibling got an implant at age 3 and is now more or less normal while the sibling who also lost hearing at age 2 but didn't get the implant until age 6 is struggling with both hearing and speech. She is able to surgically implant these devices without having done the grueling general surgery residency and also treats adults, thus breaking what we were told are the rules for choosing a specialty: (1) to cut or not to cut, and (2) do I like kids?
Statistics for the week… Study: 15 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Double date with 24-year old classmate and his wife who is studying to become a physician's assistant, followed by drinks at the new taco/tequila bar.
A brilliant energetic attending, straight-out of fellowship and with bright red hair to go along with both her specialty and patient (see below), led the introduction to hematology. Blood plasma is almost all water with an amalgam of solutes such as protein, glucose, amino acids, hormones, cytokines and clotting factors. The cellular components suspended in this plasma include red blood cells (erythrocytes), white blood cells (lymphocytes), and platelets (thrombocytes). All of these cellular components are made in mesh-like inner bone structures, bone marrow, home to hematopoietic stem cells which can become any of the cell constituents of blood in response to growth and differentiation signals. For example, if oxygen content is low or an individual has been bleeding, the kidney secretes the hormone erythropoietin (EPO) into the bloodstream to increase differentiation towards the erythrocyte (red) lineage.
Red blood cells are an engineering marvel and a story of sacrifice for a single purpose: transporting oxygen and carbon dioxide through the vascular network. Hematopoietic stem cells undergo a stunning transformation. The cell rearranges its membrane so the mature erythrocyte can survive intense deformations squeezing through capillary beds. The cell simultaneously begins to synthesize gobs of hemoglobin, which eventually will take up the entire intracellular volume of the cell. Hemoglobin is a marvelous contraption comprised of four oxygen-binding heme rings surrounded by four globin protein chains. Each of the four heme rings contains a reduced iron molecule at its center where oxygen binds. The globin chains are encoded in DNA and translated into an amino acid (protein) sequence. The protein scaffold modulates the oxygen-binding affinity to unload oxygen in metabolically active tissues. Genetic defects in globin genes can lead to hematological disorders such as sickle cell anemia. Lastly, red blood cells expel their nucleus and other internal organelles, such as mitochondria. Once completed, the 7-9 micrometer biconcave cell has sacrificed its ability to replicate in exchange for a slow but inevitable death. The average circulating red blood cell lasts no more than 120 days.
Our patient case dealt with a form of hereditary spherocytosis that first manifested in a person who had seemed to be a perfectly healthy 18-year-old. "Jessica" was an A-student, high school homecoming queen, and cross-country athlete. Early in her first college semester, a flu put in her bed for several days. After an apparent recovering, she became even more ill, sleeping all day and unable to leave her dorm. She had piercing pain in her left abdomen, her eyes began to turn yellow, and then her whole body. She was stabilized by a hospital Emergency Department and the next day saw her pediatrician back home -- like most young adults had yet to find an internist. Her pediatrician referred her to our hematologist.
The mother interjected, "This was the scariest moment for me. [her pediatrician] would not tell us what it was, although he clearly had some idea. I called the referral office, and got put on hold. I still remember the lady's recorded voice while on hold: 'You have reached the Hematology-Oncology office of ....' I was speechless! Oncology! My 18-year-old has cancer!" Our hematologist instructor continued, "Hematologists treat both cancer patients and benign blood disorders. Cancer patients almost always have hematology issues from the cancer itself, or from the chemotherapy destroying their bone marrow. I wish we could have two offices."
Jessica recounted the first appointment. "The waiting room was scary. Almost everyone was old. It smelled of chemo and death. When the doctor spoke to us, everything settled down. She said, 'You most likely have some sort of anemia, not cancer.'" Blood tests showed severe anemia. The left-sided abdominal swelling and pain was caused by splenomegaly, or enlargement of the spleen. The spleen filters the blood where resident macrophages eat old or damaged red blood cells. The macrophages recycle heme rings by releasing iron and bilirubin into the bloodstream. The yellow discoloration of her eyes and skin were from an excess of toxic bilirubin in her blood, or jaundice, a common affliction for newborn babies.
A basic peripheral blood smear showed that Jessica had premature, sometimes even nucleated, red blood cells in circulation. If the signal for erythropoiesis (formation of new red blood cells) such as EPO levels is high enough, the bone marrow will release premature cells such as reticulocytes. Her symptoms immediately improved after supplements of iron and folate, required during red blood cell differentiation for synthesis of functioning hemoglobin. However, doctors and the family were still at a loss regarding the cause of this flare-up after 18 years of perfect health.
Genetic testing showed a defect in a membrane receptor that causes her macrophages to eat up healthy red blood cells prematurely. Her bone marrow, without any iron and folate, could not keep up with the destruction of red blood cells. The hematologist theorized that the flu virus triggered the immune system to increase erythrocyte destruction. Jessica is now a normal college student. She continues to take iron, folate and recombinant EPO supplements. She gets tired easily, especially around exam time. Her school has given her a single room to allow her to get more sleep. She sometimes has mild left-sided abdominal pain. Her two brothers and sister attended. They had both opted out of genetic testing. Jessica said she has two fears: "having my spleen removed and needing transfusions to live. I've spoken to a lot of anemic patients in the waiting room who all have had to do this. I fortunately have a less severe form of spherocytosis." The class laughed as she struggled to pronounce "spherocytosis"! She ended by saying how it is important for doctors to be cheerful and energetic. She jumped out of her seat, long red hair waving, and hugged our young hematologist. "We are best friends, redheads stick together!"
I shadowed my physician for the afternoon seeing six patients: two cases of Chronic Obstructive Pulmonary Disease (COPD, typically from smoking), a pneumonia case, a two-week follow-up after a car accident, a knee injury, and a fainting teenager. The pneumonia patient was a female in her late 60s with severe dementia and under the care of the state. A caretaker brought her in with a complaint of wheezing. She could no longer speak, but could make grunting sounds. While she tried to grab the physician's genitals, we listened to her lungs and noted pulmonary edema in her right upper lung. We prescribed antibiotics.
The physician and I read the car accident patient's chart. He said, "I do not know how this patient is alive." Crashing his Ford Fusion into a stopped car at 50 miles per hour did not result in a single broken bone. He had a neck brace and terrible lacerations over his face, chest and arm, a rare success story for airbag technology given that this 65-year-old gentleman had not been wearing a seatbelt. The chart showed a history of drug and alcohol abuse, but no evidence that either was involved in the accident.
The next patient was a mid-60s grandfather who hurt his knee while playing basketball with his grandson. "Little Johnny has gotten really good. I was defending with one leg planted, and twisted. I heard a snap. I cannot put any weight on it." I performed a knee exam and noted anterior displacement of the tibia (lower leg) with the femur (upper leg) under stress. X-rays showed no bones broken. Diagnosis: torn ACL, which unfortunately cannot heal once separated. We referred him to orthopedics for an MRI and refrained from making any Vito Corleone references.
A mature and articulate 13-year old teenager presented with recurrent episodes of fainting and dizziness. She has had these episodes for over a year, but got much worse last week and had to be taken home from school twice. I walked in first and conducted an interview and brief cardiopulmonary physical. I did not note any abnormal heart sounds upon auscultation. The mother explained her theory that the fainting was caused by beginning menstruation. During the family history, we learned that four of the mother's eleven uncles/aunts had a heart defect requiring open-heart surgery. The doctor joined me. He did not hear any abnormal heart sounds but was clearly concerned by the family history. He ordered several tests and sent the child home with a visibly upset mother. I'm impatient for a diagnosis but will have to follow up via email.
"Geriatricians are a dying breed," said our lecturer the next day. "No young doctors want to treat old people." Our class supports his theory; nobody has expressed a desire to become a geriatrician. The most challenging part of interviewing the elderly for him is breaking through their fear of losing independence. Many elderly individuals will not admit if they are struggling to perform certain instrumental activities, such as driving, cooking, taking medications and even walking. Our mid-40s geriatrician stressed, "This information is the most important. Frequently, I am able to prolong their independence but I cannot help them if they do not tell me." For example, simply using a walker could prevent an all-too-common fall resulting in a hip fracture: "A third of all patients with hip fractures die within one year."
The class segued into a discussion. Classmates opened up with memories of the last days of their grandparents. One classmate's grandparents committed joint suicide shortly after being admitted to a nursing home. The geriatrician offered, "I will tell you one thing: You never want to see another horrible death once you see one. I was in the army and saw a parachuter fall. That same feeling comes over me when I see patients suffer through decisions whose consequences they do not fully understand." He concluded, "Whatever speciality you go into, you need to define what the patient wants. Physicians too often conclude clinical decisions based upon their beliefs. Some of my patients may want to live to see their grandchildren graduate school. Some just want to be able to keep walking for another year. These desires change how I care for my patient."
Several of Jane's college girlfriends descended into town for her birthday weekend, arriving around 9:00 pm. At dinner we somehow got on the topic of unions. Jane's friend was passionate on the subject of the evils of right-to-work legislation and the need to force every worker to pay union dues. It turned out that she was an intern at the American Federation of Teachers (AFT). I'll probably share her passion for unionization once I work my first 100-hour week as a resident. Jane interjected, "Shut up... today is all about me!"
Statistics for the week… Study: 15 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Movie night with Harry Potter fans to see Fantastic Beasts and Where to Find Them; Jane dragged me along.
"We live every second on the edge between bleeding to death and death by heart attack," exclaimed the young hematologist attending. She introduced us to the coagulation pathway and the lucrative and life-sustaining hematological drugs. Numerous clotting factors (proteins) are produced in the liver and released into the bloodstream. My favorites were the actions of fibrin and plasmin. Vascular damage initiates a cascade of clotting factors to cleave the precursor fibrinogen into fibrin. Fibrin acts as a sticky filament that forms an intricate spider web, binding platelets together, creating a thrombus (blood clot). This nanoscopic mesh traps everything from red and white blood cells to the numerous clotting factors such as plasmin to plug the vessel breach. Vascular remodeling and wound repair signals activate the entrapped plasmin which degrade the fibrin web through fibrinolysis.
Simply resting one's arm on a table creates cuts in the microcirculation. Our finely-tuned coagulation system is able to plug these cuts to prevent severe bleeding, while not creating too many blood clots that would obstruct flow to tissues. The hematologist explained that mutations in clotting proteins lead to uncontrolled bleeding disorders such as hemophilia (factor VI, IX or XI) and von Willibrand Disease or uncontrolled thrombosis formation such as in Leiden Factor V. She finished by explaining that vitamin K is essential for the activity of a liver enzyme that is used in the production of several important clotting factors (Factors II, VII, IX, X, numbers that become ingrained into any medical student's mind for Step I). Drugs such as warfarin target the enzyme that catalyzes the reduction of oxidized vitamin K. Without this reduction process, fewer functioning clotting factors are synthesized. This results in decreased clotting function for a given signal, the costs and benefits of which were presented in this week's patient case.
"Gerry" is an eighty year old black male who suffers from congestive heart failure after three heart attacks. "I did not treat my body well for many years." Gerry became an alcoholic in his twenties, and smoked two packs a day from his late teens through his 60s. Vodka was his drink of choice.
Gerry grew up fatherless in a crime-ridden neighborhood. "Ma did her best to raise my two brothers and me. She would whip us if we did anything wrong. She'd grab us by a leg, hold us upside down and smack away. If none of my brothers would turn the culprit in, she would whip us all to ensure the guilty got punished," Gerry reflected. "Much of my neighborhood's problem was from the destruction of the family. No one has respect for authority. When I grew up, the cops were the good guys, Ma the bad one. We grew up wanting to be cops."
Gerry described the low point in his life as returning home to see his wife and children conducting an alcohol search. "They missed the bottle that I hid in the toilet cover." He claimed that he was able to "drink a bottle of vodka before work and no one would notice." His wife divorced him after catching him driving drunk with their two girls and then his unmanaged health conditions continued to deteriorate.
Gerry began to have congestive heart failure from combined systemic hypertension (high blood pressure everywhere) and pulmonary hypertension (high blood pressure in the lungs). His second heart attack in his sixties was a wake-up call. "My doctor said, 'If you do not make drastic changes, I do not expect you will live another year.' I went completely cold turkey. I moved back home at sixty and quit cigarettes and alcohol." Gerry now lives in a retirement home. "I was very anxious about death, so much so I would be afraid to sleep in my bed. I would try to stay awake in my recliner. Eventually I realized when I go, going in my sleep is the best way. Now I sleep like an angel."
Gerry's cardiologist explained that Gerry owes his life to advances in pacemakers and fibrinolytic pharmaceutical drugs. His weakened heart, after three separate heart attacks, has less contractility. Certain areas of the his heart, such as the atrial appendages and ventricular apexes, do not fully contract. This causes "pooling" of blood or hemostasis. Still blood is more likely to form a thrombus (or blood clot). These clots, unless broken down, can travel and obstruct vessels to vital organs causing a thromboembolism. A thromboembolism lodging in a coronary artery is the most common type of heart attack; a thromboembolism lodging in a vessel supplying the brain is called a stroke. Gerry is also at increased risk of Deep Vein Thrombosis, or DVT, due to sedentary lifestyle in advanced age and poor circulation from decreased cardiac output . If a DVT in a femoral vein gets dislodged it can lead to rapid death from a pulmonary embolism, blocking blood flow to the lungs (the cause of death in at least one of our cadaver).
"Even ten years ago, the general consensus was to avoid excess bleeding," explained the cardiologist. "This has shifted to prevention of clots. You can recover from excess bleeding by getting a transfusion or IV fluids. You will not recover from brain damage from a stroke, sudden death from a PE or heart damage from a MI." Gerry and the cardiologist discussed how warfarin and coumadin are difficult to take and to prescribe because their effect varies with vitamin K input. "If my patient eats a lot of spinach one meal, it could throw the whole clotting system out of whack with drastic consequences." A new age of fibrinolytic drugs are coming that are vitamin K-independent (see eliquis ads on TV). However, this new age would not alleviate a common concern for Gerry and other elderly people: "I sometimes have trouble remembering if I took my medications in the morning if I do not put them in the pillbox. If I took my meds again at night, could this kill me? This is something that gives me so much anxiety." The cardiologist added that one occasional double dose would not kill him, but emphasized these are powerful drugs.
Jane recounted a "Women in Surgery" interest meeting she attended with other interested female medical students. A young trauma surgeon who has been an attending for three years led the discussion on the life of surgery. "Go into something else if you could be happy there. Surgery is only for people for whom nothing else would satisfy." Jane recounted the surgeon's main point: "There is no such thing as work-life balance. Anything not work becomes a distraction against surgery... Getting married, distraction. Having children, distraction. I was in surgery on my son's birthday. He waited until 10:00 pm to give me a slice of his birthday cake. His birthday was a distraction." The surgeon recounted a story of informing the parents their 17-year old child is dead. "Women cry a lot more than men. Men are usually silent. I woke up at 3:00 am for weeks thinking about that case, of what I could have done differently. Surgery never leaves you." The trauma surgeon said to wait for the surgery rotation (third or fourth year) before seeking to go into her specialty: "Most of you will be pulling your hair out on the first 24-hour shift, but a few of you will become captivated. Don't force it."
Our medical school requires students to do community service projects in six-person groups. My group chose to work with opioid addicts. The program was started by the local police department to try to fight the rise in opioid overdoses in the area. As long as there is no outstanding warrant, opioid users can bring in drugs and paraphernalia to the local police station, or a recently added clinic, and receive counseling and access to rehab programs. We met with the director, a middle-aged woman whose college son overdosed on heroin laced with fentanyl, and a nurse.
I asked how many addicts would willingly give up their drugs? The answer turned out to be three or four individuals per day. The nurse explained that based on an interview, a "program ambassador" customizes a recovery plan tapping into local, state, and federal programs: "The resources are there, just it is impossible for a non-expert to navigate them. One common complication is addicts having children. They are afraid of losing custody if they ask for help from healthcare professionals." Our group will able to serve as ambassadors once we complete an 8-hour training program.
Tuition is due this week. I have a Graduate Plus loan at 6.31 percent. There is no federal subsidy for this loan and the interest begins accruing immediately, but payments are deferred until after graduation. If I work in a non-profit health care system, i.e., most American hospitals, monthly payments are capped at a percentage of my salary. After ten years, the principal will be forgiven (paid by taxpayers!) if it hasn't been paid off. The program was designed for people who joined the Peace Corps, not for radiologists earning $350,000 per year, so there is some talk about the new Congress closing "the Doctor's Loophole.".
Statistics for the week… Study: 25 hours. With exams next week, I wish I was at this stage two weeks ago. Sleep: 7 hours/night; Fun: 1 night. Example fun: Evening watching Netflix's The Crown followed by Sunday brunch.
Exam week covered cardiopulmonary physiology, anatomy and clinical skills. Pharmacology remains the most dreaded topic. Despite this universal struggle, two-thirds of the class appear comfortable with the pace. We know what to expect. We realize that the exams are meant as a stop-safe. If one of us fails the exam, typically a score less than 60%, it is a wake-up call that we are not on-track for the final judgement: Step 1.
The other third of my classmates are nervous wrecks. They are so concerned about what they need to know that they forget about learning. Four percent of the class failed and will have to retake the exam next week. Most of these individuals had adhered to Anita's strategy of focusing on "High Yield" material, defined as material frequently included on the Step 1 exam and therefore in McGraw Hill's First Aid for the USMLE Step 1. The First Aid summary figures are worth reviewing the day before the exam, but it seems that "High Yield"-minded individuals quickly forget a substantial amount of the information. These individuals go blank during discussion of some aspect of the patient case that was in the previous block, for example, an enzyme involved in a urea cycle disorder.
As soon as the exams were done, classmates were able to reflect on their experience. We agree that the tested block was much more enjoyable than our first block, which was devoted to clinical applications of molecular pathways, many of which students were exposed to in pre-med required courses and MCAT studying. The tested block was our first foray into predominantly "clinical" material: physiology and pathophysiology. We also got to use our stethoscopes!
After my second exams, a few things I wished I knew on day one:
Most of the class reads the suggested Costanzo's Physiology ("I have a date with Costanzo tonight," is a common inside joke), but I preferred the more in-depth Medical Physiology (Boron and Boulpaep).
Twenty percent of the class no longer goes to lectures because they find it less efficient than independent study. I continue to go to hear the clinical vignettes. Some lecturers are down to an attendance rate of less than 30 percent. Maybe medical school costs could be cut considerably; Jane and and I agree that we could learn everything besides anatomy and clinical exam skills using Web-based and library resources.
The job of a medical student is to study. Many of us got through undergraduate exams by cramming the night before. This purge-in, purge-out mentality does not work in medical school. Curiosity becomes the most valuable asset in medical school. The depth and breadth of information requires constant dedication to translate understanding into retention. My search for immediate answers to questions is challenging for classmates because I don't have a smartphone right now. Jane suffers the most with my endless questions: "My ankle evertor muscles are sore. What muscles are those?" (Fibularis brevis and fibularis longus)
Statistics for the week… Study: 35 hours. The library was still packed when I left at 10:00 pm most nights this week. Sleep: 8 hours/night; Fun: Learning on Saturday that I'd passed!
We're back from our three-week Christmas and New Year's break. Our previous block was exclusively on the cardiopulmonary system. This seven-week block will cover the gastrointestinal (GI), endocrine, reproductive and renal systems.
Lectures introduced the components of the GI system, including the enteric nervous system (ENS), a network of 500 million neurons (as many as in the spinal cord!). In the 1900s anatomists dissected portions of the GI tract and tested responses to specific foods and distensions (see pioneering work by Bayliss and Starling, referred to as "The Law of the Gut"). The ENS contains afferent (sensory) neurons that possess mechano- and chemo-receptors that sense the lumen of the gut. These afferent neurons send their information to interneurons that synapse (connect) with efferent (response) neurons. Efferent neurons control smooth muscle tone and secretory gland cells. Drugs that affect neural synapse communication can affect GI function: I saw a patient abusing opioids hospitalized because he had not defecated in over three months.
The autonomic nervous system integrates with the enteric nervous system, relaying information from the central nervous system, which includes the brain, but the ENS can function independently.
We learned the embryological origin of GI organs: the liver, pancreas, spleen and lungs are all outgrowths of the same tissue! Classmates had a lot of questions and after-class discussions about the fetal twisting of the gut tube that produces these organs.
Lectures also covered the basics, e.g., peristalsis: when a bolus of food enters the lumen of what doctors call the gut, a continuous tube from esophagus to stomach to intestine to rectum. Sensory information is integrated in the myenteric plexus, a region of dense nerve activity that travels between the smooth muscle layers. Efferent neurons contract circular smooth muscle about two centimeters proximal to the distension. Simultaneously, efferent neurons relax distal circular smooth muscle. This ring of contraction propagates and moves the food about five centimeters before being succeeded by the next wave.
Anatomy lab kicked off with the dissection of the abdominal wall. We saw the numerous fascial layers that separate the abdominal muscles and the peritoneum. Every cadaver had six-pack abs once we removed the fat covering the rectus abdominus. Rectus abdominus is a superficial muscle that runs from the lower sternal border and ribs to the pubic tubercle (bony prominence in the front of hip). The muscle alternates between a muscle sheath and three or four horizontal tendinous lines creating six-pack or eight-pack abs.
We were told to concentrate on understanding the inguinal ligament, the division of abdomen from the legs, and inguinal canal. There are two routes for vessels to enter a lower extremity: under the inguinal ligament to the anterior leg or through the pelvic cavity into the posterior leg. Groups with male cadavers showed classmates dissecting female cadavers how the vas deferens takes sperm through the inguinal canal into the abdominal wall and down into the pelvic cavity to connect to the urethra. Sperm travel right next to the peritoneum membrane which encloses the intestines. My favorite trauma surgeon commented that interns and residents are selected to determine the hernia type by feeling up the patient's scrotum into the inguinal canal.
Three classmates and I stuck around through the lunch break to watch a GI surgeon attending dissect a "Fem-Fem". The cadaver had an obstructed left femoral artery. A tube was inserted into the left femoral artery distal (farther away from the origin) of the blockage and connected to the perfused (supplied with blood) right femoral artery. It felt like a hard rubber tube, not what I imagined for a biologically compatible material. I asked if this tube would cause stenosis (hardening) of the attached arteries. He said, "Eventually, but this man's comorbidities would likely kill him within two or three years, well before stenosis. This was a way for him to keep his leg for his last years."
Our patient case: "Jenny," a beautiful, intelligent 35-year-old female. After college she moved to start work at an advertising firm. She began to lose weight steadily despite a normal diet. She had regular diarrhea and terrible acne. "The acne was by far the most debilitating. It made me severely depressed," explained Jenny. "And the dermatologist was worthless." After the dermatologist's suggestions did not work, she proposed putting Jenny on Accutane. She declined because of the potential for depression due to interactions with her anti-anxiety medications. She lived with the acne and diarrhea for five years.
Seemingly overnight, everything changed. Jenny lost thirty pounds in a month. Her hair fell out. She developed painful bruises on her legs. "My coworkers thought I was crazy. I thought I was dying."
A new doctor tested her for celiac disease, and, after a positive result, referred Jenny to the Gastroenterologist who came to present her case. The physician, a woman in her 40s, explained, "Five years is quite typical for time until diagnosis following the onset of celiac symptoms. It wasn't on physicians' radar ten years ago." Celiac disease is an autoimmune disease triggered by gluten, an abundant protein in wheat. Gluten survives the acidic environment of the stomach and is phagocytosed by macrophages in the small intestine. In normal individuals, this elicits a small inflammatory response. Individuals with MHC gene variants may experience an aggressive immune response that destroys the gut epithelial lining. Due to the damage to the lining of her intestines, Jenny was unable to absorb essential vitamins and nutrients, which caused malnutrition and anemia.
Jenny worked to adjust her diet in the pre-gluten-free label age: "I called up every manufacturer and asked if the food contained gluten. Brand-loyalty was key." Adhering to a gluten-free diet, she is now the healthy mother of a healthy boy. "It is what it is. It is much easier now with labeling and I find my whole family eats healthier." A student asked the doctor, "What is the difference between celiac disease and gluten-sensitivity?" The doctor chuckled. "I have many patients who tell me they feel better when they do not eat gluten. I tell them good for you. It is not because of an immune response from gluten. It is probably because they just eat healthier food." Jenny chimed in, "I do not understand people who eat gluten-free foods that are 100-percent carbohydrates. How is that healthier?"
In lecture, a neurobiologist introduced the role of glial cells in regulating cerebral blood flow. Glial cells are the non-neuronal support network for neurons. Astrocytes, a type of glial cells, surround 98% of the surface area of the brain's capillary network forming the blood-brain barrier. They decide what gets in and out. We learned about current trends in astrocyte pathology. Glioblastoma, cancer of glial cells, is one of the most aggressive forms of cancer. The cancer cells migrate along blood vessels to expand to other areas of the brain making It incurable by surgery. While migrating, the cancer cells scrape off the adherent astrocytes giving the voracious cancer cells direct access to the leaky capillary and its nutrients. As it migrates along the vessel, astrocytes are unable to re-adhere to the vessel causing fluid to leak into the brain's microenvironment. This is theorized to be the cause of seizures in patients with glioblastoma.
Alzheimer's is another area he believes involves dysregulation of astrocytes. Unlike most tissues, brain blood flow is regulated both at arteriole and capillary levels. Evidence shows astrocytes are able to constrict capillary networks, but amyloid plaques lead to stiffening of the capillary, which interferes with this control mechanism.
I asked him about a recent 60 Minutes episode, "The Alzheimer's Laboratory", about families in Colombia with genetic early-onset Alzheimer's, based on church records going back to the 1800s. Children of an affected parent have a fifty percent chance of losing memory and independence in their thirties or forties. However, from this tragedy comes opportunity for researchers and future Alzheimer's patients. There is currently no effective treatment for Alzheimer's, which has thus become America's most expensive disease, about $240 billion in 2016 and set to grow as Americans age.
"This represents a critical juncture in Alzheimer's research," he explained. "Although amyloids are the only target of all drugs in the research pipeline, there is no evidence that amyloid plaques actually cause Alzheimer's. Some cases have tons of amyloid plaques, some none. Some people have tons of amyloid with no Alzheimer's." The 60 Minutes show described a clinical trial investigating whether a monoclonal antibody against amyloid can delay early-onset Alzheimer's. I was reminded of another neuroscientist's comment: "If a clinical trial fails they first blame the patient cohort, second the timing of therapy, and only then the science."
Statistics for the week… Study: 18 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Dinner with Jane's visiting family before a Saturday morning 10K through 4 inches of snow.
30 classmates rented a ski lodge a two-hour drive away. Most did not go skiing but they still managed to have a grand-ole time, perhaps because they'd packed two car trunks full of peppermint schnapps.
Lectures detailed the absorption mechanisms of the gastrointestinal system. The sodium-potassium ATPase pump creates the electrochemical gradient that energizes transport of glucose and amino acids. (See next week for how the kidneys use almost the exact same proteins to get rid of waste.)
Stretch and presence of food causes G-cells in the Antrum of the stomach to secrete the peptide hormone gastrin. Gastrin acts directly on parietal cells to secrete hydrochloric acid into the stomach lumen. In case those cells don't respond adequately, gastrin also acts via intermediary enterochromaffin-like (ECL) cells that release histamine, which in turns activates parietal acid secretions. Eating complex macromolecules, rather than simple refined sugars, may activate more levels of regulation for processing.
Every day before anatomy lab, Jane and I watch the corresponding Acland videos, fascinating dissections by Robert Acland, the late surgeon and clinical anatomist who developed important microsurgery techniques. We get so enthralled by these that we have to stop ourselves from watching too far beyond the upcoming dissection.
This week we opened the peritoneal cavity, revealing the stomach, intestines, liver, pancreas, and spleen. Several cadavers, including mine, had appendectomies. My group's liver felt rock solid due to cirrhosis. One cadaver had sigmoid colon volvulus: her sigmoid colon had twisted around itself, causing pressure to build up and stretching the typical 1.5-foot section to three times the normal diameter and twice the length. It looked like a massive caterpillar. One student stepped out due to nausea as her group accidentally sliced the colon, causing feces to ooze out. That's something we didn't see Robert Acland do.
A pediatric surgeon joined my anatomy group. She was was wonderfully helpful with a story to go along with every structure. She commented that our cadaver had been good for GI surgeons, with at least three abdominal surgeries: appendectomy, hysterectomy, bariatric surgery (stomach stapling). Darwin was interested in the origin of species; GI surgeons look at the "origin of appendixes." Surgeons look for an odd triangular fat fold at the ileocecal fold to locate the appendix during appendectomies.
I stayed late with the surgeon to dissect the vessels near the pancreas, which is nestled in among the stomach, spleen, and transverse colon. "Never touch the pancreas," she explained. "In surgery, all those pancreatic digestive enzymes can leak out and start digesting organs." I cut the pancreas to reveal the deep structures behind. I saw how the splenic artery runs with the pancreas to the spleen. The splenic vein then travels across the pancreas to fuse with the inferior and superior mesenteric veins to form the massive portal vein. Working in the cramped space gave me an appreciation for why pancreatic cancer is so difficult to remove surgically.
Our patient case: "George," a 55-year-old combat veteran with a history of alcohol abuse, pancreatitis (inflammation of the pancreas), and liver cirrhosis. He presented with jaundice, clay stool bowel movements and dark orange urine. These symptoms pointed to issues with the liver and pancreas for our differential diagnosis. Blood work showed vitamin deficiency and anemia. An x-ray revealed a pancreatic tumor mass obstructing the Ampulla of Vater. This prevented pancreatic enzymes and bile from being secreted into the duodenum of the small intestine. In a healthy person, bilirubin, the toxic product formed from recycling red blood cells' hemoglobin, is transferred into the duodenum with bile from the liver. Gut bacteria convert this into stercobilin which is excreted in feces giving it its characteristic dark color. George's obstruction caused a buildup of bilirubin in extracellular tissue, blood and urine. The tumor was inoperable and he was referred to hospice care, where he passed away after eight months.
George's wife came in to discuss her experience along with a nurse and a social worker who had managed George's "home-care hospice" case. The nurse manages 10-15 patients and makes up to 5 home visits per day. Many of these visits are pain management emergencies. A student asked if there was ever an issue with opioid abuse? She responded, "We err on the side of the patient. If the patient tells us there is an issue we listen. The prescriptions are for two-week periods." She explained that prescription is typically methadone, a slow-release opioid which has less addiction potential, but in the last year the hospice facility has tried to tighten control of opioids. "I dealt with one case this year where the family was stealing pain pills from granny."
"You are the gateway to hospice care," continued the nurse. "Saying there is nothing more I can do as a physician for a patient that you may have been caring for decades is heartbreaking. The patient transitioning from aggressive care with hope to comfort care is similarly heartbreaking for the family."
George's wife described how helpful hospice care was for her family. She described being crushed by the immense requirements for medical appointments and medications during chemotherapy. "We had no time to think about what comes next. We had no chance to enjoy the time he had left." George was able to live at home for his last eight months. The case manager described how hospice care allows families to plan and come together: "When the white flag goes up people have time to adjust. An estranged brother or daughter will travel to reconnect with the family." The nurse added, "People think someone in hospice care is going to die within a week. That is simply not the case. Most are there for several months to even one-and-a-half years."
The case manager added that hospice centers have coordinated care with other facilities to meet a patient's needs. "If a patient's last wish is to go to the beach, we'll coordinate care with a local facility." The team will typically attend a patient's funeral.
One student asked about assisted suicide. Although illegal in this state, the nurse believed it should be a terminally ill patient's choice. Some do ask about getting transported to Michigan or other states where it is legal. The nurse commented how one Huntington's patient made the decision to starve to death. George's wife commented how George considered assisted suicide. "He would never take his own life but he did ask about assisted suicide. If it wasn't for me and his son, I believe he would have done it." The panel concluded by stressing the need to have end-of-life discussions with patients early, before terminal disease states, and promoting patients to have an advanced directive (or living will).
At lunch our class discussed the cost and quality of end-of-life care. More than 80 percent of patients living with a chronic disease claim they want to avoid hospitalization and intensive care during the terminal portion of their illness. However, in 2005 the CDC estimates that only 25 percent of deceased died in their own home. In 2008, Medicare spent $55 billion for the last two months of patients' lives (CBS). One-quarter of Medicare expenditures are for care in a beneficiary's last year of life, an unchanged ratio from twenty years ago.
The next day, the state's chief medical examiner gave a lecture on opioid abuse. "Sherry" is a trained pathologist who conducts autopsies on suspect deaths and public health crises (at a much lower salary than if she were practicing).
According to Sherry, heroin use became widespread in the 1960s when addicted Vietnam veterans returned home. Poppies were cultivated in Vietnam. The 1980s cocaine boom caused a decline in heroin. "We have Kurt Cobain to thank for bringing back heroin with 90s Grunge."
"You will quickly realize that today's opioids are nothing like yesterday's heroin when you go on your ED [emergency department] clinical rotation," explained Sherry. "You'll see several ODs in a given night." In 2013, drug overdoses became the U.S.'s number one cause of unintentional death. Heroin is found in urban centers whereas pills are found in more rural and suburban areas.
"Street" heroin used to be cut to 6-7 percent purity, thus requiring intravenous injection to get high. This drove Hepatitis C infections, which Sherry said have declined due to access to clean insulin needles from Walmart and the increasing purity of heroin. Today's 20-percent-pure heroin can be snorted: "Without the needles there is no social stigma." Sherry said that students are trying heroin in the same way that older generations might have tried alcohol and marijuana. 1 in 13 high school students in our area admitted to using heroin.
"Do not touch any bag or foil you might find in the ED!" Sherry exclaimed. "If you touch it, you could overdose and die." Synthetic opioids are now so powerful that some act through absorption through the skin. Pure heroin is about twice as potent an agonist (binds to mu-receptor producing "high" response) as morphine. Fentanyl, quite widespread now, is 100 times as potent as morphine. "The new rave is carfentanil. Addicts are quite excited about this one, 10,000 times as potent as morphine and used to put elephants down. Drug labs and health workers are petitioning for access to the opioid-blocker Narcan in case of skin contact with carfentanil."
"Drug dealers are actually quite brilliant businessmen," Sherry explained. "They realized the demand does not go away after the prescriptions are cut off. Police try to suppress the names of individuals who overdose because users will look for his or her dealer. The overdose means that the product must have been good.Some dealers purposefully overdose a client because it boosts sales."
A student asked what she would recommend doing to prevent this epidemic. "Death penalty for heroin dealers," she laughed and continued, "Loved ones see the signs of drug abuse but they do not realize how serious they are. With the potency and variability of drugs these days, you can overdose on the first high, or the hundredth high." She also cautioned us that the gateway to addiction is frequently prescriptions from physicians. The individual who overdoses is on several prescriptions: antidepressants, anti-anxiety, sleep. "These are people connected to the healthcare system. These mental illnesses present as physical pain such as back pain. It takes one doctor to overlook the mental cause and prescribe painkillers for the physical pain."
Sherry said that prescription opioid abuse has been reduced by prescription monitoring networks. "A few years ago, drug addicts were able to state-hop because these monitoring networks would not talk across state lines."
Statistics for the week… Study: 18 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: drinks at classmate's apartment with about 10 other students, followed by the downtown bar scene (everyone else) and home (me and Jane).
Goodbye gastrointestinal system; hello renal system. I was only two-thirds of the way through the GI textbook chapter.
Lectures introduced how the kidneys regulate body fluid "compartments." The body contains about 42 liters of water: 28 liters intracellular (within cell membranes) and 14 liters extracellular (outside cell membranes). The extracellular fluid includes 11 liters of interstitial fluid (between cells) and 3 liters of blood plasma. These compartments are constantly changing their equilibrium with excretion of urine and intake of food with varying osmolarities (concentration of solution). Western diets high in salt increase the osmolarity of blood, causing a net increase in blood volume and increase in blood pressure for a given vascular tone, also known as volume-loading hypertension.
In Anatomy we continued dissection of the abdomen, removing the liver, spleen and kidneys. Liver removal required five scalpel cuts, each of which took about five minutes to prevent damage to surrounding tissue. The liver is anchored in the body by several strong ligaments: hepatogastric, hepatoduodenal, hepatodiaphragmatic and falciform. The falciform ligament connects the liver to the anterior abdominal wall including the belly button. Ligamentum teres, the remnant of the umbilical vein, runs through the falciform.
There are five regular Anatomy instructors, three of whom are surgeons and two are veterinary anatomists(!). However, our school also brings in three or four working surgeons. This week my favorite trauma surgeon noted how in some conditions the umbilical vein remnant can reopen! Two groups were scolded for ripping the hepatoduodenal ligament without dissecting the portal triad (portal vein, common bile duct and hepatic artery). Our cadaver had no gallbladder, so we worked with other groups to understand that region.
Next we removed the kidneys, slicing each into anterior and posterior sections. Most kidneys had large renal cysts, one the size of a golf ball embedded in the cortex (outer region), and some included stones ranging in size from sand grains that one could feel up to two centimeters in diameter.
Every day we bombard our body with a variety of food and water with different concentrations. It is up to our kidneys, the interface between the vascular system and the urinary tract, to maintain electrolyte and volume homeostasis (equilibrium).The urinary tract is a continuous, branching tubular network that extends from the urethra to the bladder to each kidney's ureter. The ureter branches into microscopic collecting ducts. Each collecting duct connects to hundreds of nephrons (specialized tubule segment). The nephron tubule segment ends at Bowman's capsule, a spherical bulge in the tubule and the glomerulus (specialized capillary network). Each kidney has about 1-1.5 million nephrons.
It is here at the glomerulus that blood plasma spills into the tubule system becoming filtrate. Under normal physiological conditions, the kidneys receive 20 percent of the cardiac output. Every day 180 liters of plasma is filtered by the tubule system. However, normal urine output is about 1.5 liters per day. That is an immense amount of reabsorption of solutes and water!
The glomerulus is the first step in deciding what becomes urine. The glomerulus supports the beautiful "foot processes" of podocytes, amazingly specialized epithelial cells (see the details in this Nature article). During kidney development, the distal (far) end of the nephron tubule, which becomes Bowman's capsule, is penetrated by blood vessels, which become the glomerular capillaries. The glomerular endothelial cells begin to loosen their connection with each other to form fenestrated ("fenetre" meaning windows) capillaries. The tubule epithelial cells interacting with the capillary endothelial cells become these specialized podocytes. The cell body of a podocyte sends thousands of "foot processes" to wrap around the capillary cylinder. Proteins on the podocytes' cell membrane bring these foot processes together to create slit diaphragms, the final filter pore of 10-20 nanometers in diameter. For blood plasma to reach the urinary tract, it traverses through the fenestrated glomerular capillaries, a dense extracellular basement membrane and and the podocytes' slit diaphragms. This multi-layered biological nanofilter filter prevents large particles and negatively charged proteins from entering the tubule.
The plasma that is filtered becomes filtrate. Unlike the epithelial cells of the more distal urinary tract, the epithelial cells of the nephron are highly specialized in transport processes. Along the way the epithelial cells of the tubule reabsorb filtered solutes (e.g, sodium, glucose and amino acids), secrete waste products (e.g., protons and urea) and determine how much water should be reclaimed back into the vascular system. The kidney is under sensitive hormonal and nervous control to regulate plasma osmolarity and plasma volume. If blood volume decreases, baroreceptors in the carotid bodies signal the kidney to increase isosmotic absorption via aldosterone. If blood osmolarity is too high, the hypothalamus (part of the brain) signals the pituitary gland to release Antidiuretic Hormone thereby increasing free water reabsorption (urine concentration).
Sound complicated and failure-prone? It is. Most hypertension and other nominally vascular disorders start with dysregulation or degradation of the kidney. Our nephrologist professor: "The kidney allows terrestrial life."
Our patient case: "James," an 18-year-old freshman at the local community college. James presented to his primary care physician with fatigue, general weakness, and hepatosplenomegaly (enlarged spleen and liver). Lab tests revealed a low platelet and white blood cell count. He was prescribed antibiotics and referred to a hematologist: earliest appointment in two weeks.
His symptoms worsened with swelling in his feet and periorbital (around the eye) region. His mother took him to the ED, where a physician, suspecting a reaction to the antibiotics, swapped the antibiotics for an antihistamine to combat the inflammation. At the appointment the next day, the hematologist suspected mononucleosis (the kissing disease "Mono") but the test came back negative. He was referred to a nephrologist: earliest appointment in three weeks.
"The appointment made me put the symptoms to the back of my mind. I would deal with it at the appointment." James gained twenty pounds in water weight with swelling extending to his lower extremity and scrotum. The nephrologist ran tests that showed extremely low albumin levels in his blood plasma. Albumin is the most abundant plasma protein. Without this oncotic (protein solute) pressure, there was a net movement of water out of James's plasma into the interstitial fluid. Why was his albumin so low? The nephrologist said, "You are either peeing out an unbelievable amount of albumin, or your liver is not able to produce it." He suspected Hepatitis C or HIV.
What would peeing gobs of albumin out look like? The nephrologist told James that it would look like frothy urine: "Imagine whisking egg whites with water." James responded, "I always thought frothy urine was normal. It's all I have known." He was sent straight to the ED.
James's kidneys were shutting down. While in the hospital, blood pressure spiked from 150/90 to 250/150. Doctors thought he might not make it. He underwent plasmapheresis (filtering of plasma through a machine) and plasma transfusions for two straight days. "I was really drugged up but I do remember seeing my blood being pumped through these tubes out of my body. That was the first time I was scared."
James stayed in the hospital for nine days. "I did not sleep for two days straight. Every two hours a nurse would come in to check my blood pressure and take blood." He was most frustrated that he was not allowed to shave or shower: "My platelet count was so low they thought I might bleed to death if I cut myself." A kidney biopsy revealed inflammatory vascular deposits in his glomerular capillaries. He was diagnosed with Systemic Lupus Erythematosus, an autoimmune disease that causes destruction of various organs including the kidneys. He was put on short-term immune suppressors and glucocorticoids, which are anti-immune steroid hormones.
James's recovery was long and painful. He had 45 lbs of excess water weight. He would urinate clear fluid every 30 minutes. Water seeped out of a cut on his left leg. Three months after discharge he resumed classes. "I wrapped a washcloth around the cut to soak up the water that still seeped out." My legs were so swollen I could not bend them to walk up stairs. The severity of his disease did not hit him until after the critical episode.
The mother was thankful for his post-diagnosis medical care, but angry about the three-week wait between the hematologist and nephrologist. James's nephrologist said that if the appointment had been even one day later, James would have not recovered normal kidney function, if he even survived the severe electrolyte imbalance and hypertension.
James is now considered cured, though he remains on immune suppressors. His kidney function has returned to normal. James hopes to become a biochemist developing new drugs.
Later that day, the head of the ED introduced emergency medicine, the art of triaging undifferentiated patients and sending diagnosed patients to specialists for care. Straight out of a three-year residency, EM physicians make an average salary of more than $310,000. Salaries at academic institutions are lower, while salaries tend to be higher for more rural institutions. EM physicians work 30-32 hours a week with regular shifts. "Once I am off, I am off. I don't carry a pager. I do not have any patients once I am off my shift." A more rural and less busy ED will have 12- or 24-hour shifts; a busy urban ED will have 8-10 hour shifts. He loves going rock-climbing and skiing on weekdays: "The slopes are clear at 11:00 am on a Tuesday. Internists and surgeons claim they have hobbies, but if you ask them how long it has been since they did that activity, it is usually months. Ask an EM physician and the answer is 'Last week'."
The physician said that emergency medicine is the youngest speciality. In the 1940s, a critically ill patient would be brought to the family physician. Formal recognition of emergency medicine as a specialty came in the early 1970s.
Any downsides to the specialty? "Other specialists have no respect for EM physicians. We are a jack-of-all-trades, master of none." EM physicians are required by federal law to see all patients. "We do not get to pick our patients." EM physicians also get no appreciation from patients. "The patient sends the fruit basket to his cardiologist after a heart attack, even though it was the EM physician that saved his life. Instead, we get lawsuits. Patients don't sue their internist they have been seeing for a decade when their condition deteriorates into a heart attack. They sue the ED."
Our school's full-time chief diversity officer, a Ph.D. in psychology, hosted a lunchtime diversity discussion with catered Indian and Thai food. Sadly I was forced to miss this event due to shadowing a physician in the hospital. Classmates said the main topic was diversity in the classroom. Fortunately this was not my last chance. The chief diversity officer's assistant sent an email this week inviting students to a self-defense class:
Students who identify as female: Learn maneuvers to help you evade uncomfortable and/or dangerous situations. … Students who identify as male: Learn tips on how to engage in a situation and diffuse it without escalating it.
Statistics for the week… Study: 15 hours. Sleep: 8 hours/night; Fun: 1 night. Example fun: Medical school formal, also known as "MedProm" at a downtown ballroom. The medical school deans and instructors left around 10:00 pm, perhaps because the social chairs hired a DJ specializing in electronica and hip-hop. We danced to Lil Jon's "Get Low" and the pop hit "Closer". One of my favorite classmates and his wife brought hip flasks of liquor to spice up the cash bar concoctions.
In anatomy lab, we investigated abdominal blood vessels. The descending aorta pierces the diaphragm at the aortic hiatus to enter the abdomen where it is now called the abdominal aorta. (The external iliac artery becomes the femoral when it passes into the leg***. Being a medical student is like driving in Massachusetts where roads adopt new names every time they cross over a town border.) The abdominal aorta gives off numerous branches: the arteries of the gut (celiac, superior mesenteric and inferior mesenteric), the paired renal arteries and the gonadal arteries (testicular or ovarian). At the umbilicus (belly button) the abdominal aorta bifurcates into the right and left common iliac arteries. Each common iliac artery branches again into the internal and external iliac, which supply the pelvis and the leg, respectively. One group from last week thought they had an aortic aneurysm that was causing all the organs to be pushed forward in the abdomen. It turned out to be cancer (source unknown). They could not find any of the structures in our lab manual as the cancer mass had engulfed everything.
Our trauma surgeon, a woman in her 60s, described a frequent patient case involving the portal system (vessels that direct blood from the gut to the liver), which we dissected this week. An alcoholic presents to the ED for severe rectal bleeding or esophageal bleeding. A CT scan (Computed Tomography or 3D X-ray reconstruction) reveals liver cirrhosis, an enlarged portal vein, and tortuous blood vessels all through his GI tract.
Most blood supply to organs drains into the inferior/superior vena cava which drain into the right atrium of the heart. In a healthy person, blood supplying the GI tract (colon, intestines, spleen, pancreas, stomach and distal esophagus) drains into the portal vein. The portal vein drains into the liver for detoxification. Blood leaves the liver through the hepatic (liver) vein, which drains into the inferior vena cava to join the normal circulation.
The patient's liver cirrhosis (hardening of the liver) caused severe portal vein hypertension (high pressure). Blood seeking an outlet drains into the lumen of the gut tube instead of through the portal system. "Portal hypertension can cause bleeding worse than getting shot in the aorta," said the surgeon. "This is a life-or-death situation."
Lectures continued detailing transport processes of the renal system. We learned about several drugs to treat diabetes mellitus (not to be confused with diabetes insipidus, a hormonal disease preventing urine concentration). Diabetes is named for the accompanying diuresis (excessive urination). Diabetes mellitus (mellitus means honey-sweet) is named due to the high glucose levels present in the blood plasma and urine.The severity of diabetes can be categorized as "insulin-independent" and "insulin-dependent". Insulin-dependent diabetics require injected insulin to keep glucose levels down.
One of the most effective drugs for diabetes mellitus is metformin, which inhibits natural production of glucose from energy stores (gluconeogenesis). Metformin, derived from the French lilac (Galega officinalis), can prevent or at least delay type 2 diabetics transitioning to insulin dependence. Since at least the 1800s, this plant has been used to treat individuals with polyuria (frequent urination). By far the most common complaint is the terrible breath from metformin. The toxicologist brought a small dummy infused with metformin breath. Sally the Future Surgeon was sitting next to the dummy and threw up after five minutes. "You try to go on a date with this breath," exclaimed the toxicologist. "Good luck!" Metformin has terrible compliance rates.
(A few hours later we were surprised when the conference room we'd planned to use was occupied by the apparently-forgotten dummy. We vacated the premises, with the smell chasing us down the hallway.)
Farxiga (Dapagliflozin), approved in 2014, is a fascinating drug for the treatment of diabetes. Farxiga inhibits SGLT, a glucose pump protein, used to reabsorb glucose in the kidney back into the blood. Patients just pee out glucose as blood plasma spills into the urinary tract. Unfortunately, this leads to unbearable urinary tract infections; bacteria love sugar.
The toxicologist brought in various insulin pens and even bought a bottle of insulin and needles. Apparently low dose insulin can be purchased over the counter although it is quite expensive. Insulin is measured in standard insulin "units". (One unit refers to the amount required to lower glucose a set amount.) $150 for a 10 mL bottle at 100 units/mL. This might last some patients a week, others a few days. "Some severe insulin resistant diabetics use 300 units a day."
Our patient case: "Sherry", a 50-year-old female who has had type 2 diabetes since her late twenties. Since childhood she has been overweight, but never obese. Her whole family had a history of type 2 diabetes.
Sherry's poor management of her diabetes led to kidney failure.(Diabetic nephropathy, degradation of the glomerulus caused by hyperglycemia, is the number one cause of kidney failure.) She joined the ranks on the dialysis wards. Dialysis filters a patient's blood by pumping the blood through a semipermeable membrane. On one side of the membrane is the patient's blood; on the other is a dialysis fluid (basically saline). Solutes such as glucose and electrolytes diffuse down their concentration gradient into the dilute dialysis fluid. Each dialysis session can use up to 30-50 liters of water!
Sherry described how close she got with her dialysis group. She elected to do overnight sessions. "It's hard to get much sleep with everyone chattering and all the noises from the machines. We had a good group." Sherry initially went only three times a week, thus requiring a large volume of blood plasma to be removed (some people go five times per week). This caused terrible cramps and muscle weakness. Fortunately, Sherry's federal employee insurance covered home dialysis treatment and she was able to switch to a five-times-a-week schedule in the comfort of her own home. An entire room in her house was dedicated to the fluid tanks, filled monthly by truck. Because most dialysis patients have a port (brachial artery-vein autogenous fistula) installed, at-home dialysis can be done without help from a technician, but the procedure is supposed to be done when someone else is in the house in case the patient passes out.
Sherry went through seven years of dialysis. "I was at the store when my doctor called me. 'Can you get to the hospital in 24 hours?'. 'Yes! Yes!' I screamed." Sherry matched. She had a kidney donor.
"You can only appreciate this gift once you have experienced dialysis for several years. I know several transplant recipients who quickly get their kidney and just throw it away after a year. They use their new life to drink, party and have sex. They end up back in the dialysis centers. No wonder why there is strong disapproval of kidney transplants at the dialysis centers." Sherry had retired from the federal government due to the time commitment of dialysis, but now she works part-time.
Shadowing my physician mentor this week, our first patient turned out to be a classmate. I excused myself. I also diagnosed my first patient! A 45-year-old male presented with right leg pain worsening with exertion. I asked him to lie on the examination chair and remove his pants. I then palpated his sciatic nerve, which caused a terrible radiating pain down his leg. Diagnosis: Piriformis syndrome. The sciatic nerve exits the pelvis into the thigh through a tight hole called the greater sciatic foramen. Piriformis, a muscle used for lateral rotation of the leg, can become inflamed and enlarged. This constricts the sciatic nerve causing radiating pain. He asked, "How do you make it stop?" I replied, "Let's ask the doctor when he comes in." Turns out there is not a great remedy. Medicine is better at labeling problems than treating them. Anti-inflammatory medications such as Tylenol and ibuprofen may help. The key is rest. Unfortunately, "George" is a construction worker without health insurance. He makes too much to be on Medicaid, but not enough to afford Obamacare premiums. I felt terrible sending him home knowing that he couldn't afford to rest and would soon be receiving a shocking bill from the clinic.
About 20 percent of the class, and some of the faculty, went to the local women's march, and Type-A Anita ventured to Washington, D.C. for the main event, explaining that she was demanding "equal rights for women."
At lunch after the march, there was what would have been a discussion among eight classmates about campus sexual violence (it fell slightly short of an actual "discussion" due to the lack of interest in hearing dissenting point of views or facts that didn't fit preconceived opinions). All supported the school-run administrative tribunals that have been expelling accused students since the 2011 "Dear Colleague" letter from the Obama Administration. Several students argued that by matriculating at school you agree to abide by the school's code of conduct. If the school's tribunal or committee deems an accused guilty of violating that code, that individual can be expelled without violating due process. Two classmates compared this to accusations of sexual harassment in the workplace. "A business can fire an employee if he or she is accused." Anita: "There are far more rape cases than false accusations. 1 in 5 female college students are sexually assaulted on campus. It would be unbearable for her to live in the same dorm and go to the same class as him."
Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Late night bar shenanigans on the pretext of a classmate's girlfriend arriving in town.
We began endocrinology, the study of hormones. Hormones are signaling molecules, namely peptides and cholesterol derivatives, that cause systemic changes in the body. The pea-sized pituitary gland sits in a small alcove at the base of the skull, right behind the nasal cavities near the optic nerve. This master regulator of hormones functions as the interface between the brain and the blood, secreting nine different hormones.
The pituitary is actually two separate organs. The posterior pituitary gland, more recently renamed the neurohypophysis, is a protrusion of neurons in the hypothalamus. These neurons release oxytocin and antidiuretic hormone (ADH) into systemic circulation (the blood). For example, ADH is released in response to an increase in the concentration of solutes in the blood, thus causing the kidneys to concentrate urine by reabsorbing free water into the blood. Other neurohypophysis neurons release oxytocin (a.k.a. the love hormone) during labor causing uterine contractions and also while a baby nurses causing a "let down" (spray) of milk. (New mothers can have excruciating cramps from uterine contractions during nursing because of this oxytocin release).
The anterior pituitary or adenohypophysis is a broken-off extension of the mouth that wraps around the neurohypophysis. These cells also secrete hormones under the control of the hypothalamus. These hormones regulate everything from the thyroid and adrenal glands to the menstrual cycle and milk production. Thyroid issues are some of the most common adult ailments. The thyroid gland, located right under the "Adam's apple" secretes thyroxine. Thyroxine increases metabolism and "energy". Our endocrinologist says that many of her patient's request synthroid (synthetic thyroxine) to help lose weight. Low thyroxine levels can not only be caused by an issue in the thyroid but also by the pituitary. The pituitary secretes thyroid-stimulating hormone (TSH) which tells the thyroid to release thyroxine. Without TSH, there will be no thyroxine even if thyroxine levels are abnormally low.
Our patient case: "Susan", 22-year-old female presenting with fatigue, blurred vision, transient loss of vision, and a headache. Labs show abnormally low thyroid stimulating hormone (TSH) and low thyroxine and abnormally high prolactin levels for someone not breastfeeding. She was referred for a head MRI.
The MRI revealed a large mass in the pituitary. Susan had a prolactin-secreting adenoma of the adenohypophysis. The mass was squeezing her optic nerve causing the vision problems. She underwent transsphenoidal (through the nasal cavities) surgery to resect (remove) the pituitary gland. Her vision returned to normal, but she will require hormonal supplementation for life.
This presented an enormous challenge for Susan. Susan's husband was on SSDI. Her children had health insurance through Medicaid. Susan was the only one working and also the only one without health insurance because she didn't get it through her employer. Hormone supplements are expensive. Unless she withdraws from the workforce and qualifies for SSDI and/or Medicaid, she and her doctor will endure a lifelong struggle to decide what hormones to prioritize. Growth hormone? Synthroid? ADH?
An epidemiologist introduced clinical trial research. We investigated survival metrics and clinical trial studies on mesothelioma, a cancer of connective tissue, most commonly of the pleural membrane surrounding the lungs. Average survival is 12-20 months after diagnosis; five-year survival is less than 5 percent. The largest risk factor for mesothelioma is exposure to asbestos. Production of many industrial products such as paint, brake-pads and ships used to include asbestos fibers. "It isn't only males who get mesothelioma," explained the epidemiologist. "When Daddy got home from the shipyard, Mom and Daughter would run to the door and wring out Daddy's coat. Asbestos was on that coat."
We got on the subject of whether the National Institutes of Health (NIH) disproportionately funds cancer research. A traditional successful cancer drug trial finds a few months of additional life compared to the current standard of care, but if funded by a pharmaceutical company does not take into account quality of life. For example, a clinical trial for a VEGF inhibitor in the treatment of renal cancer increases median overall survival (OS) from 21.3 to 23.3 months compared to IFN plus placebo. What if the quality of life for those 23.3 months is miserable compared to the quality of life for the 21.3 months under the current standard of care? "Patient-reported outcomes is the big buzz word in clinical trial research. Double-blind trials are essential for these subjective metrics."
The whole school is abuzz about Trump's seven-country immigration ban. Classmates post on Facebook about their immigrant roots (mostly grandparents or farther back in the family tree). One classmate posted a link instructing what to do if a "Customs" officer comes knocking on your door. The reply: "Did you mean immigration officer?"
Statistics for the week… Study: 25 hours. Sleep: 8 hours/night; Fun: 1 night. Example fun: class bbq followed by classmate's performance at local coffeeshop! They performed a now class-favorite Twistin and Groovin from Leon Bridge's Tiny Desk Concert.
Reproductive lectures start this week. "Males will finally understand how much harder females have it," joked a female classmate.
There are three main parts of the reproductive system: the internal genitals, external genitals and gonads (testis or ovary). A quick theme that emerges is female development is the default: unless some signal overrides this process, female parts will emerge.
Gonad (testes; ovaries): Primordial germ cells (PGCs) are some of the first cells that are formed after fertilization. PGCs have the potential to become any cell in the body including sperm and eggs. These cells end their migration at the genital ridge, a paired region in the right and left lower abdomen. Here, the PGCs interact with surrounding cells to form the gonad.
In females, each PGC differentiates into an oocyte (egg) that cannot replicate. The surrounding cells nurture each egg in a single follicle. These eggs lie dormant until puberty.
In males, the presence of a functional Y chromosome overrides ovary development. The SRY gene on the Y chromosome signals for the surrounding cells to form interweaving tubes of Leydig and Sertoli cells. Have you ever thought about why the testes are outside the body? Evidently, spermatogenesis (production of sperm) requires a lower temperature than body temperature. Thus production of testosterone by Leydig cells leads to the descent of the testes. My favorite embryology professor instructed, "Boys, don't drive with the seat warmer on for a long trip. It'll kill your sperm!" The testes are pulled out of the abdominal cavity through the inguinal canal (see prior chapter). This descent is typically complete a few weeks before birth, but may take as long as one year after birth. [At birth this canal is not sealed completely, which can cause an indirect hernia. Structures, typically small intestine, can squeeze through the inguinal canal and potentially into the scrotum! Infants are routinely checked for this disorder.]
Internal Genitalia (epididymis, vas deferens and prostate; uterus and fallopian tube): In females, an embryological remnant of the kidney forms the fallopian tubes, uterus and proximal (to cervix) vagina. These tubes must fuse together and the septum must be removed to form a normal uterus. Failure to remove the septum is not uncommon (~3%). A more serious defect is if the tubes fail to fuse completely resulting in a bicornuate uterus with two distinct cavities connected at the cervix. Both are still able to become pregnant but have a much higher risk for complications and miscarriages.
In males, a similar tube forms the epididymis, vas deferens and prostate. The vas deferens transports mature sperm from the testis through the inguinal canal into the abdomen. The vas deferens then descends into the pelvis to form an ejaculatory duct. The ejaculatory ducts open into the prostatic urethra (urethra section with the prostate surrounding it).
External genitalia (penis; vagina, labia minora, labia majora, clitoris, etc.): At six weeks post-fertilization, the undifferentiated external genitalia appear, namely the genital tubercle and genital swellings. There is no way to differentiate male from female at this stage, just that normal development is occurring.This transformation all takes place in the perineum (square region formed from the pubis, ischial tuberosity (bone you sit on) and coccyx (pointy ). We quickly appreciate how crowded this area is -- the rectum, bladder and, in females, vagina/uterus all lie in this small volume. Initially, the urinary tract and anus share a common lumen. A septum forms to separate these into the anus and the urogenital openings.
My classmates and I learn this dense region differently. I have found focusing on embryology helps me. Each component of the undifferentiated external genitalia gives rise to the respective female and male reproductive parts (see Netter's, page 364). Therefore, each part has a homologue (typically with similar function) in the opposite sex. For example, the prostate in males which wraps around the urethra is analogous to the Gland of Skene in females (thought to be involved in female ejactulation). The genital tubercle will form into the glans of the penis or the glans of the clitoris. The glans is supported by erectile tissue and vascular tissue that engorges during sexual arousal.
Males fold each of these parts together as evidenced by the raphe, or ridge, noted on the ventral side of the penis all the way to the anus. Classmates laughed on learning that the anatomical terms for parts of the penis make sense only when the penis is erect: the ventral penis is the underside with the urethra; the dorsal penis faces up.
Looking at the above in real life: Anatomy lab was short. Most students left within an hour. We investigated the external structures of the male and female cadaver. One group found an undescended testicle that got stuck in the inguinal canal. It was far smaller than the descended testicle. The trauma surgeon did not notice any evidence of testicular cancer. She said, "He and his doctors most likely knew he only had one testicle. Today we would remove the undescended testicle at an early age.
In lecture, an internist introduced the male genitourinary (GU) exam before we practiced on dummies. He joked, "I still remember my introductory lecture on the GU exam. I remember the pictures. I was scarred by the pictures." He continued this tradition by showing us images of foreskin infections and noted that "the most common reason 20-year olds come in to the office is for penis problems."
The internist described a common reproductive defect: hypospadias is where the urethral meatus (opening of the urethra) in not at the tip of penis but along the shaft or even in the scrotum. He amplified on what we had seen in anatomy lab with 10 minutes on cryptorchidism, the failure of a testicle to descend into the scrotum at birth. An undescended testicle is infertile due to the higher temperature and carries an elevated risk of testicular cancer. If a testicle is not descended by age 1, the current standard of care is to remove it. The physician then asked the class, "What is the number one type of cancer in 20-year-old males?" Despite having been prompted by the lecture topic, nobody in the class was able to come up with the correct answer: testicular cancer.
We discussed 5-alpha reductase deficiency (5-ARD), a rare genetic disorder commonly referred to as güevedoce. The phallus of the penis forms under stimulation of 5-alpha dihydrotestosterone (DHT), a more activated form of testosterone (same compound that causes male baldness). DHT initiates enlargement of the paired vascular tissue (corpus cavernosum, crus of the penis) and the erectile tissue (bulb of the penis, corpus spongiosum). Females have analogous parts, just they have not folded onto each other, nor enlarged. 5-alpha reductase is the enzyme that converts testosterone into DHT. This prevents the enlargement of the phallus in utero. Las Salinas, Dominican Republic, is known for having a high prevalence of 5-ARD: 1 in 90 XY males are born with ambiguous genitals and raised as females. However, during puberty 5-ARD individuals have such high testosterone levels that the ambiguous clitoris enlarges into a penis. Hence güevedoce or "eggs at twelve". The community holds coming-of-age parties for these chosen individuals. 5-ARD individuals can be fertile propagating this genetic defect through generations in the isolated village. On the bright side, these individuals do not worry about male baldness.
The most dreaded part of the male GU exam for physician and patient is the digital rectal exam. The prostate can be palpated by pushing on the anterior rectum with two digits. Enlargement or masses can be felt. However, the internist emphasized that only the lower third of the prostate can be felt. "The digital rectal exam cannot rule much out." An ultrasound exam of the prostate can see much more without associated distress.
One student asked what the medical consensus is on circumcision. The internist replied, "There is no medical reason to get or not to get circumcision. The main medical argument is the increased risk of foreskin infection with poor hygiene. However, with good hygiene, there is no increased risk of infection." He ended by asking, "Why do doctors ask patients to turn their head and cough?" The cough increases intraabdominal pressure that accentuates any inguinal hernia. "We ask patients to turn their head cause we don't want to be coughed on…"
Statistics for the week… Study: 20 hours. Sleep: 8 hours/night; Fun: 1 night. Example fun: watched college basketball at the house of an M2 (second-year medical student). She is married to an engineer and they're debating when to have kids. The current plan is for her to give birth during the third year of medical school so that she isn't pregnant during residency.
Five hour-long lectures over three days on calcium regulation to control neuronal activity, coagulation, heart function, and bone structure. One challenge is that calcium is a cation (positively charged ion) that can come out of solution. Too much calcium will cause calcium precipitation with various anions (negatively charged ions) potentially causing thrombosis of vessels, kidney stones, and coma. Too little calcium will cause hyperexcitability of neurons with the classic Trousseau sign.
Calcium in your body is governed by mass balance: What comes in must come out to maintain equilibrium levels (flux in = flux out). Calcium intake varies, so calcium efflux adapts accordingly. Two hormones, parathyroid hormone (PTH) and 1,25 dihydroxycholecalciferol (vitamin D) regulate calcium homeostasis through the gut, the kidney and the massive calcium reservoir of bones. (Calcitonin used to be thought to play an important role, but, at least in adulthood, appears secondary to PTH and vitamin D.)
The parathyroid glands, four small tissue regions within the thyroid in the neck, release PTH in response to decreased extracellular calcium. PTH instructs the kidney to increase calcium reabsorption and decrease phosphate reabsorption. The decrease in phosphate is thought to prevent precipitation of calcium-phosphate crystals. Further, PTH increases the kidney's conversion of inactive 25-hydroxycholecalciferol reserves into active vitamin D. Vitamin D primarily acts on the intestines to increase calcium and phosphate absorption. Both PTH and vitamin D act on bone cells to fine-tune bone maintenance.
Bone is an organized mesh of specialized bone cells, blood vessels, extracellular proteins and mineral crystals (primarily hydroxyapatite). There are three main types of bone cells: osteoblasts (bone-building cells), osteocytes (imprisoned osteoblasts), and osteoclasts (bone-destroying cells). Osteoblasts secrete various proteins, primarily collagen, into the extracellular environment that form osteons (nucleation site for mineral deposition). As the osteons become mineralized, the osteoblasts, now termed osteocytes, become imprisoned in this mineral matrix. Osteocytes communicate to each other with cellular foot processes, forming the elaborate osteocytic membrane.
The osteocytic membrane forms a cellular interface that separates the mineral deposits from the vascular network: bone on one side, blood vessels on the other. Therefore, the osteocytes can regulate the “bone fluid” to determine net bone resorption or deposition. If osteocytes pump calcium and phosphate from the blood into the bone fluid, net bone deposition occurs in this microenvironment; if the osteocyte membrane pumps calcium and phosphate out of the bone fluid into the blood, net bone resorption occurs in this microenvironment. Activated osteoclasts secrete enzymes and acid that degrade the osteon proteins and the mineral deposits, respectively. Although overactive osteoclasts lead to weakened bones, transient osteoclast activity is needed to make stronger bone by making room for more densely packed osteons. Perhaps next year I will understand enough to relate osteocyte and osteoclast activity.
Bone development and maintenance require adequate calcium input (1200mg/day), steady levels of vitamin D (greater than 30 IU/mL), and mechanical stress signals. One of the most overlooked bone health tools is weight-being exercise, the mechanical stress of which is sensed by the imprisoned osteocytes, inducing bone formation.
Our patient case: Lucy, 60-year old female artist with a history of kidney stones presents to the ED for a femur fracture after a fall. In addition to having broken the largest bone in her leg, a CT showed microfractures in several additional bones. Blood work showed extremely elevated PTH despite hypercalcemia (high calcium levels in the blood). Presence of a parathyroid adenoma, a benign tumor that secretes PTH, is suspected. Physicians recommend the removal of Lucy's parathyroid glands, a parathyroidectomy.
Lucy suffered from several psychological diseases in childhood and had become a fervent believer in holistic medicine. Lucy's internist explained, "It's always a challenge to emphasize how these complementary approaches are complementary, not supplementary. The Internet has introduced patients to a lot of information. Some good, some bad." The internist explained that Lucy is one of her favorite patients despite the extra time required for each visit. "She would bring me stacks of articles on supplements I had never heard about. We would dig to find the active ingredient. I've learned a great deal from her." Lucy tried several herbal, yoga and acupuncture therapies for osteoporosis and joint pain. A student asked the internist, "When do you draw the line if a patient does not want to follow your recommendation?" She responded, "If a patient is not following my advice I don't boot them out. I ask myself, 'Would another physician have a better outcome?' The only patients I have kicked out were ones that forged my signature on prescriptions." After several months of holistic treatment, Lucy elected to get the parathyroidectomy. Her calcium levels have come down and osteoporosis, measured by bone mass density, has improved. Although this was a success for our healthcare system, Lucy was diagnosed with breast cancer six months ago.
Instead of dissection (anatomy lab), we went to a radiology workshop. My classmates describe radiologists as "antisocial people who sit in a dark reading room all day with $40,000 monitors." The consensus among our class is that this profession is at risk of being replaced by image-recognition algorithms. Only one of our classmates, a quiet Asian-American gentleman, admits he would like to be a radiologist. Our lecturer is a father of two whose phone repeatedly buzzed with a toddler's voice saying "dada" as the ringtone. "I teach one class a month, and this is the day imaging blows up," exclaimed the radiologist. The radiologist was quirky, but sociable and self-deprecating. He did mention his monitors at least twice: “they cost as much as your tuition!”
Although the software that can replace a radiologist with 12 years of training is purportedly around the corner, our workshop was derailed when we were not able to log into the Picture Archiving and Communication System (PACS) due to a recent software upgrade being incompatible with the browser. After the school's entire IT staff swarmed in to update the browser, we were up and running. I greatly enjoyed investigating abdominal and pelvic anatomy on de-identified patient CT and MRI scans.
The radiologist showed a CT angiogram (CT with contrast agent injected into arteries) of "nutcracker" syndrome, in which the left renal artery is compressed by the superior mesenteric artery and aorta due to a lack of retroperitoneal fat. It turns out too little fat can be a bad thing! Nutcracker syndrome is diagnosed by radiologists and fixed by surgeons. He spent ten minutes examining different imaging planes to convey the complex anatomical relationships.
Statistics for the week… Study: 16 hours. Sleep: 8 hours/night; Fun: 1 night. Early bedtime for Jane and me. We competed in a 5k. We both got first place in our age group, perhaps because the competitive runners elected to do the 10k. Drinks with our favorite couple (classmate and his PA-student wife) that evening.
"This is for 3,000 years of patriarchy!" exclaimed a female classmate as she slices off the penis. Today we are dissecting the external genitalia. We noted the three main regions of the penis: left corpus cavernosum, right corpus cavernosum, and corpus spongiosum.
Lectures introduced the female reproductive cycle, also known as the hypothalamus-pituitary-ovarian (HPO) axis.
This topic requires us to learn the derivatives of cholesterol and the enzymes that catalyze these conversions (graphic). Cholesterol is a 27-carbon structure that gives rise to numerous signaling molecules such as androgens, estrogens, progesterone, aldosterone (isoosmotic antidiuretic) and cortisol. When discussing cholesterol signaling, there are two questions: What enzymes are found in what cell? How much access does the given cell have to low-density lipoproteins (LDL) in circulation?
Two-thirds of the class is memorizing the names and important enzymes in First-Aid that will be tested on Step I. For example, they memorize 17-alpha hydroxylase deficiency will lead to increased aldosterone and cortisol levels with decreased sex hormones and ambiguous genitalia. They aren't trying to learn the structure of cholesterol. I am wishing them good luck in retaining that information for next year.
The cells of the body have an ability to make fine distinctions among these related cholesterol-derived compounds. For example, aldosterone is very similar in structure to glucocorticoids (e.g., cortisol). So similar that kidney cells' aldosterone receptors have an affinity to cortisol. However, the aldosterone receptor is typically near an enzyme that degrades cortisol into cortisone which has a lower affinity. In this clever way, the aldosterone receptor can maintain its high sensitivity (percent true positive) to aldosterone while increasing the specificity (percent true negative). [After you enjoy a bag of licorice, it is possible to have transient psuedohyperaldosteronism, including hypertension and hypokalemia from cortisol activating the aldosterone receptor; licorice inhibits the activity of the enzyme that degrades cortisol into cortisone.]
The menstrual cycle is divided into the ovarian cycle (follicular and luteal phase) and the uterine cycle (proliferative and secretory phase). Different regions in the hypothalamus release pulses of Gonadotropin-Releasing Hormone (GnRH) into the pituitary portal system. GnRH activates gonadotroph cells in the pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH) into the systemic circulation. FSH and LH act on ovarian follicles.
Each follicle is surrounded by granulosa cells that nurture a single dormant egg. Outside the granulosa cells are connective tissue called theca cells. LH binding to theca cell receptors initiates a signaling cascade that increases cholesterol uptake into the cell and increases transcription of the enzymes required to convert cholesterol into androgens. These androgens diffuse out of the cell and suppress further development of the follicle.
FSH binding to granulosa cell receptors upregulate aromatase, the enzyme that converts androgens into estrogens. Granulosa cells do not have the enzymes to synthesize androgens (estrogen precursor) themselves. Follicles are selfish. Once FSH has selected a follicle it will suppress other follicles from maturing, thereby ensuring only one follicle ovulates each cycle.
As FSH increases aromatase activity in granulosa cells, estrogen levels rise throughout the follicular phase of the ovary. Estrogen has many effects including proliferation of the uterine lining (proliferative phase of the uterus). Estrogen also has negative feedback on the neurons in the hypothalamus controlling GnRH release and negative feedback on the gonadotropins in the pituitary. Every 26-32 days in a healthy female, estrogen levels reach such high levels that the negative feedback switches to positive feedback. (The mechanism of this about-face remains a mystery to medicine.) The positive feedback produces the LH surge, a massive release of LH and FSH from the pituitary, initiating ovulation.
Ovulation is the rupture of the follicle. The oocyte or egg is released into the peritoneal cavity (space between abdominal wall and visceral gut organs) where the fimbriae of the fallopian tube sweeps it into the fallopian tube. Fertilization typically occurs in the ampulla of the fallopian tube and is carried into the uterus for implantation. An ectopic pregnancy occurs when a fertilized egg implants anywhere outside the uterus, most commonly in the fallopian tube. However, our embryology professor mentioned it is possible to have implantation in the peritoneal cavity on the the connective tissue of the gut.
After ovulation, the follicle enters the luteal phase. The ruptured follicle becomes the corpus luteum, a highly vascularized endocrine structure. Before, only the theca cells had adequate access to cholesterol in the bloodstream. Now, the granulosa cells have abundant access to cholesterol from LDL in the blood. Granulosa cells lack the enzyme to convert cholesterol into androgens. They are able only to convert androgens into estrogens and cholesterol into an androgen precursor, progesterone. Thus, progesterone levels spike initiating the secretory phase of the uterus. The uterus is ready for implantation of a fertilized egg. If fertilization occurs, the placenta secretes HCG (a close analog of LH) which preserves the corpus luteum production of progesterone. If fertilization does not occur, the corpus luteum involutes (degrades) causing progesterone withdrawal. This sudden decrease in progesterone causes shedding of the uterine lining or menstruation. The decline in progesterone and estrogen disinhibits the GnRH pulsations initiating the whole cycle again.
Two-thirds of the males had at best a fuzzy knowledge of the menstrual cycle. For example, how long is it? When do menses takes place in relation to ovulation? About half of the women did not know how their birth control works. Classmates argued about whether males should be given a handicap for the reproductive block: "You females have it easy. We've never seen this stuff before."
Our patient case: Gina, 31-year-old overweight female presenting with amenorrhea (lack of periods) and hirsutism (hair growth on chin, armpits, etc.). A pregnancy test is negative. A hormone panel reveals high levels of estrogens, androgens and LH.
Gina suffers from Polycystic Ovarian Syndrome (PCOS). PCOS is named for the ultrasound appearance of small cysts in the ovary. Confusingly these fluid-filled sacs are not "ovarian cysts," but simply mature follicles that are unable to ovulate. The elevated levels of androgens inhibit further maturation of follicles and ovulation and cause hair growth. The endocrinologist explained that hair growth, especially on the chin and neck, is what brings women to her office: "The amenorrhea is alarming but it is not what typically brings them in."
PCOS affects about eight percent of reproductive age females, although there is not a standardized diagnostic criteria for PCOS and the causes are not fully understood. Diabetes and obesity are known risk factors: adipose (fat) tissue produces androgens, which interfere with follicle maturation. The inability to menstruate is serious. The uterus is stuck in proliferation mode, which vastly increases the risk of endometrial (lining of the uterus that regenerates every cycle) cancer.
How do we get Gina to ovulate? The endocrinologist explained how every woman's HPO axis is different. "It's really trial and error." Gina, like many women with suspected PCOS or infertility issues, undergo a progesterone challenge. A high dose progesterone injection is given initiating the transition from the proliferative phase of the uterus (high estrogen, low progesterone) to the secretory phase of the uterus (high progesterone). Once progesterone is metabolised, progesterone withdrawal should initiate menses. This confirms that the problem is an inability to ovulate.
Gina is taking clomiphene, a drug also used to treat infertility. Clomiphene inhibits estrogen receptors in the hypothalamus to prevent estrogen negative feedback. Therefore, there continues to be release of GnRH and downstream release of FSH despite the presence of estrogen at levels which should cause negative-feedback . Clomiphene increases the risk of twins as multiple ovulations may occur. Gina also underwent what sounds like a barbaric procedure called ovarian drilling. A needle inserted laparoscopically destroys various follicles in a random array. Ovarian drilling is quite successful in decreasing androgen levels and inducing ovulation. Gina still is not on a normal cycle, but has been menstruating. She is trying to get pregnant with her husband.
[See also "Small-sample Behavioral Economics" for how clomiphene may be taken by women with normal fertility.]
Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: One of our classmates recently moved in with two males in their 20s. Her new apartment is a bachelor pad equipped with a pool table, beer pong table, dart board and xbox. After two weeks of straight exam study, she was demonstrating her social skills by hosting a 26th birthday party for another classmate.
"Lactation: Use it, or lose it" is our theme for two days. A family physician brought in one of her patients, a 30-year-old mother of two. When four-month-old "Nora" got hungry, she whipped her breasts out in front of the whole class. The physician explained that the breasts are made of 4-18 glandular ducts with suspensory connective tissue and fat. The baby needs to be rotated using different positions (e.g., the football hold) to ensure each duct is used.
Two hormones are important for lactation. Prolactin, secreted by the anterior pituitary gland, signals the glandular ducts to produce milk. If the ducts begin to build up in pressure, prolactin secretion will be inhibited. Once this cascade has begun, it is almost impossible to reverse the spiral, which is why breastfeeding in the first days after delivery is critical. Although prolactin produces milk, oxytocin (the love hormone) causes the release of milk. When a baby is on the nipple, the ducts contract, producing a let down. Other signals, such as a baby crying,can cause oxytocin release. We were fortunate enough to see a let down: Milk shot out of the nipple for several inches and sprayed all over the baby's face and clothes. Nora was loving it.
"Breastfeeding should last for at least six months and up to one year plus/minus two months." The physician continued, "A child will let you know when he or she is ready to wean. The child will start grabbing solid foods and teething on the nipple." Current conventional wisdom, confirmed by the most heavily cited studies, is that breastfeeding for at least six months (1) builds mother-child bonds with oxytocin release, (2) decreases the child's risk of obesity, increases IQ, improves immune system function and improves social skills, and (3) decreases the mother's risk of breast and ovarian cancer.
The family physician noted that her specialty, increasingly rare in American cities, is the only one that follows both mother and child during pregnancy, labor, and after birth. "This allows a whole different perspective that used to be the norm. In most big city hospitals, the moment after delivery, the infant is whisked away by the pediatrician, while the mother is followed up by the Ob/Gyn. Family medicine bridges this patient divide by caring for both mother and child and sometimes grandmother too."
On the advice of yesterday's physicians, Americans abandoned breastfeeding in favor of formula. On the advice of today's physicians, Breastfeeding rates are back up to roughly 50 percent and are tracked by the CDC. The mother explained how difficult breastfeeding was for her first child. "If it was not for my physician, I would have quit after one month." She developed a severe case of mastitis (inflammation of the glandular ducts caused by an infection or obstruction). "Every time I breastfed, I would cry in pain." The worst thing to do for mastitis is to stop feeding. Instead, you should feed or pump in short pulses. The physician noted, "A big misconception about breastfeeding is that it should not hurt. It will hurt. A lot." In addition to the biting, oxytocin release in the first few weeks can cause painful uterine contractions similar to the experience of labor. The physician continued to explain the difficult decisions her patient's face without extended maternity leave. "They ask themselves, 'should I quit my job to breastfeed, pump, or switch to formula?' Each presents challenges especially if the pump is not covered by insurance, or if the family gets insurance through their job." (This seemed to support Ivanka Trump's observation that motherhood has become the primary obstacle to women's professional advancement, but Anita still isn't in a positive mood about any Trump family member.)
The physician noted how there exists a black market for milk, especially for colostrum. Colostrum is the milk produced in late pregnancy that is rich in antibodies and protein. Our modern range of reproductive technologies, including surrogacy, has produced the largest number of families in which an infant is present and yet no adult is capable of lactation. "Colostrum is worth more than gold!"
That evening I attended an optional workshop on women's health led by three female physicians, one of them an OB/GYN specialist. Fifteen students, including five men, from different years showed up. We practiced inserting different intrauterine devices (IUDs) in dummies. IUDs are shaped like a "T" with arms that spring out when deployed, thus anchoring the device in the uterine horns. The IUD is connected to two strings that exit the uterus through the cervix. A physician can pull on the strings to remove the IUD. The strings are trimmed during insertion so that they end just outside the cervix, which enables women with IUDs to check the strings every month to ensure the device has not been displaced. None of my classmates with IUDs knew that they were supposed to do this.
The first IUD marketed was Teva's Paragard. "Paragard is the most cost-effective contraceptive ever created," noted the gynecologist. Paragard uses copper to kill sperm before they can reach the egg for fertilization. It is is effective for ten years. Most women are choosing Skyla and Mirena, a progesterone IUD. These are more expensive but women like it because of the decreased bleeding. One family physician with experience with adolescents noted, "Paragard has this unfortunate misnomer that it causes heavy bleeding. It's just a woman's normal cycle. The progesterone IUDs give lighter bleeding. Some women on Skyla or Mirana stop having periods altogether." I asked if older or younger women are more receptive to IUDs versus normal birth control methods. She responded, "Younger women (under 25) are by far more resistant to IUDs. They don't want anything in their body but they want to have plenty of sex. I have to beg them to use some form of contraceptive."
A pediatric gynecologist gave two lectures on puberty. My favorite fact: fifty percent of healthy adult weight is added during puberty. Females begin puberty, on average, at age nine with the growth spurt, followed by thelarche (breast development) at age 10 and finally menarche at age 12.5. These ages are delayed in larger families, higher altitudes, and rural settings. Males begin puberty, on average, at age 11 with an increase in testicular volume. This is followed by pubic hair, the all-important growth spurt, voice changes, axillary hair, the ability to ejaculate, and fertility. The class chuckled when he commented, "Males are shooting blanks for a bit. Males can ejaculate before fertility."
In his practice, he evaluates "precocious puberty". He deems puberty premature if the child reaches a stage three or more years before normal. The most severe cases are generally due to a hormone-secreting pituitary adenoma. Some of his patients undergo the growth spurt and menarche at age six. Black children typically undergo puberty 1-1.5 years before risk-adjusted white children. "My colleagues in other countries have it easier. Race cohorts are not as meaningful in the US because of genetic and ethnic mixing. Other countries these 'normal' numbers are more relevant."
A week before exams and the library once again is crowded. Students stare at laptops (with peeks at an open Facebook window) or textbooks. The librarian brings her 12-cup coffee machine out for students to use during exam week. About half of us bring mugs while the rest walk across the street for Starbucks.
Pharmacology is a huge part of this exam and memorizing drug names is one of our toughest challenges to date. A friend's mother advises companies on drug names, which may reflect millions of dollars of analysis. Names that "flow" are easily remembered: gliflozin is a typical suffix for drugs that make glucose flow in the urine (SGLT2 inhibitor); glutides keep the GLT1 incretin tide coming on. Classmates say that they are enjoying TV drug ads a lot more than they used to.
Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: 1 day. Example fun: Jane and I ran a 5k trail run.
Exam Week: physiology (including pharmacology), anatomy, and clinical (x2).
Classmates are nervous about physiology due to range of systems covered in this block: endocrinology, reproductive, kidney, and gastrointestinal. From our class GroupMe chat: "I cannot believe they could not put one of these systems into the next block." (We can believe anything about the next block because we haven't experienced it!); "FML," [F… My Life] liked by 26 classmates.
Anatomy questions were easier than on the previous two exams. Every question was first order (e.g., What is this structure?), instead of a more challenging clinical scenario or applied reasoning (e.g., Which of the following structures would be used to access the posterior aspect of the stomach?). The most difficult question asked us to identify two arteries in the abdomen on a CT image slice. Classmates speculated that standards were lowered in response to complaints during the last block regarding the anatomy curriculum. I wasn't among the dissatisfied; if I get a well thought-out question wrong I tend to remember the material.
I spoke with an M4 (fourth-year medical student) after the anatomy exam. The school apparently used to conduct the anatomy exam in the lab on your individual cadaver. They stopped this because some students felt under too much pressure from being "pimped" by instructors and "it did not look good for the LCME [Liaison Committee on Medical Education]." I asked, "What does pimping mean?" The term refers to an attending bombarding a resident or medical student with questions. The M4 chuckled, "Hospitals have not succumbed to these restrictions so be prepared on your rotations. A good attending won't let his or her resident leave the day without feeling humbled or inadequate, depending on how you take the experience."
After exams we completed a Web-browser-based anonymous evaluation for every instructor. The "Learning Environment" section requires a response to "Were you required to perform any personal services?" and "Did you feel you were denied opportunities for training or subjected to offensive remarks because of gender, ethnicity, or sexual orientation?" We were informed via mass email to be careful with this section because every "yes" response causes an email marked "urgent" to be sent to each dean. Accidental "yes" responses at the end of the last block caused a bit of an inbox meltdown among the academic administrators.
The good news about "offensive remarks" is that LCME requires they be recorded, along with the rest of each lecture, on video. This way students who can't be bothered to attend still have access and anyone who enjoys being offended can repeat the experience. Over half the class uses this feature and our large IT staff are frequently called to help with issues. Before the weekend, a student asked a beloved instructor, "What is your favorite beer?" He responded, "The video is recording, I'll tell you afterwards."
Statistics for the week… Study: 25 hours. Sleep: 8 hours/night (I once again get more sleep during exam week?); Fun: 1 night. Example fun: Final exams ended at 12:00pm. Ten of us went to classmate's apartment for beer and mimosas, followed by an early happy hour excursion downtown and late night dancing. Jane and I slept until noon the next day.
We had a week off. Several classmates visited girlfriends, boyfriends, and family. One went on a Caribbean cruise. A few stayed in town to recuperate and study this next block in advance ("gunners" is the class label for this behavior).
We'll study neurology for the next two months, but class began with two deans reprimanding us. "It has come to our attention that several doctors and professors think you need to work on professionalism. Several of you are on Facebook, browsing Amazon, and checking Instagram during lecture while you sit next to a physician. SnapChatting in class is inexcusable. These physicians frequently volunteer their time to come in and speak to you. Treat them with respect. Every class gets a reputation. Don't let this be yours."
For eight weeks we will be taught almost exclusively by a 74-year-old neuroanatomist, "Doctor J". He worked for several years as a physical therapist, then earned a Ph.D. in neuroscience. His first slide was a quote from Emerson Pugh: "'If the human brain were so simple that we could understand it, we would be so simple that we couldn't." "We will do our best," explained Doctor J. His second slide was a black and white photo of an old guy. "Neuroscientists bow before Cajal." In the late 1800s there was no consensus on the anatomy of the nervous system. Two luminary anatomists, Camillo Golgi and Santiago Ramón y Cajal, supported opposing viewpoints. Golgi supported the reticular theory: nerves are a syncytium of several cells connected together. Cajal supported the neuron theory: each nerve is a single cell. Cajal used Golgi's own staining method to disprove the reticular theory. This history lesson gave a human spin to the evolution of knowledge. These men worked in shoddy laboratories with microscopes that we could build today out of paper and tape.
We had to purchase several tools for the neurological exam, including a reflex hammer, pen light, and eye chart. Our white coat is filling up with gadgets! We will practice the exam in several workshops. Students complained to the dean about Doctor J not posting answers to the workshop questions. The neuroanatomist responded during lecture, "This is your fault. The first few years we did give out answers for the lab book. I put a copy in the library. Within a week, someone had photocopied it and send it as PDF to the whole class. The value of the workshops went down, no one attended, so I no longer give the answers out." Apparently not all classmates were mollified by this explanation because enough students went back to the dean that he submitted a "formal grievance" against Doctor J.
Lecture began with an overview of the nervous system, divided into a central nervous system (CNS) and peripheral nervous system (PNS). The CNS is a tube with a hollow canal in the middle where cerebrospinal fluid flows. This tube is simple in the spinal cord but becomes suddenly more complicated at the top of the tube, which will become the brain. During fetal development (in utero), the cells of this part grow much faster than the surrounding skull causing bending and folding of the tube. The brain retains its lumen (inner membrane adjacent to canal) as the four ventricles of the brain that are continuous with the central canal of the spinal cord.
Unbeknownst to me, the spinal cord does not extend the whole length of the spine. Before birth, the spinal cord extends to each vertebrae. However, during childhood the vertebrae elongate faster than the the spinal cord, resulting in the spinal cord's termination at the first or second lumbar vertebrae (above the hip bones). A lumbar puncture ("spinal tap"), a common procedure to sample cerebrospinal fluid, leverages this anatomy by sampling the cerebrospinal fluid at L4 without the risk of puncturing the spinal cord.
There are about 860 billion cells in the brain, only 10 percent of which are neurons. Ninety percent are supporting cells called glia and microglia. These cells perform various functions: astrocytes (a type of glia) maintain the blood-brain barrier by wrapping foot processes around ninety-five percent of the capillary surface area (it reminds me of the scintillating podocytes in the glomerulus of the kidney); oligodendrocytes (a type of glia) insulate the axon cable (wire to the next neuron(s)) by wrapping sheaths of their cytoplasm around the cable; microglia are specialized resident macrophages that get in the central nervous system in utero before the blood brain barrier is formed.
Myelination is essential for neuron function. The conduction velocity of the action potential (the nerve signal) decreases as the resistance of the axon cable increases. Organisms such as the giant squid without myelinating cells achieve high transmission speeds by having huge axon diameters. Myelination decreases the effective membrane capacitance, which reduces the amount of potential needed to charge up the axon, and decreases potential leakage. Myelination enables the preservation of high speed as more neuron connections are packed into a small volume. This is important because intelligence is related to the connectivity (or synapse density) of each neuron. A human brain is estimated to contain more than 100 trillion synapses for roughly 86 billion neurons.
We learned how the number of cells change during human development. Between the third week and twenty-eighth week after fertilization, 250,000 brain cells are produced every minute! Many of these neurons undergo apoptosis (cell suicide) during training of the neural network. Despite this amazing proliferation, the brain is only twenty-five percent of its adult size at birth; the brain reaches seventy-five percent of its adult size at one-year of age.
In my small group we discussed foundational neuroanatomy structures. The corpus callosum is a bridge for nerve fibers to cross between cerebral hemispheres. Someone mentioned the corpus callosum is thicker in females. A question "Is this why women are more emotional?" yielded chuckles from several male students and glares from Type-A Anita and straight-shooter Sally. Anita replied, "Yes, that is exactly why. It's going to be a long two months with you guys."
Anatomy held a dry lab in which we felt bone vertebrae. Dry vertebrae (just the bones) have spinous processes which look like something out of a Game of Thrones episode. The spikes you can feel on your back are these spinous processes. The vertebral body, the main weight-bearing part, lies deep to this on the anterior (front) side. The spinal cord sits between the vertebral body and the spinous process inside the vertebral foramen (hole). The spinal cord gives off spinal nerves through the small bilateral intervertebral foramen. We saw how the intervertebral facet joints differ among the cervical, thoracic, and lumbar (neck, chest, and lower back) regions. The cervical vertebrae have the joints in the axial (horizontal) plane facilitating rotation; the cervical have the joints in an oblique plane preventing significant movement here; and, the lumbar vertebrae have their joints in the sagittal (vertical side section) facilitating forward bending and extension.
Our patient case: Jonathan, 25-year-old male presents to the ED nine months ago for a three-minute seizure and worsening headaches in the morning for the past month. A neurological exam shows absence of venous pulsations, suggesting elevated intracranial pressure. Jonathan did not pay much attention to the headaches. He was busy at work, and his wife was due with a second child.
A CT ("CAT scan") revealed a 3x3x3 cm (a little more than a cubic inch) tumor in the right temporal lobe of the brain. Surgery was scheduled immediately. The neurosurgery team debated removing the entire temporal lobe or just a "lesionectomy" where they remove the tumor with as good margins as possible. A lesionectomy was performed and a pathology analysis of some of the tumor removed revealed a grade III glioma. Jonathan's neurosurgeon told us that "All grade III gliomas eventually become grade IV." A death sentence. Jonathan is still alive, nine months after his first ED visit, but was unable to attend due to worsening health.
According to the neurosurgeon, a patient presenting to the ED with a headache will always get a head CT. However, it is unlikely the same patient's primary care doctor will order a head CT for just a headache.
How many patients with advanced brain cancer elect not to get surgery? “Much more rare than you would expect," responded the neurosurgeon. "Everyone hopes they will be the exception, the extreme outcome. We hope for a cure, so our treatment plan is very aggressive.” He has operated on a 86-year-old with grade IV glioma (the patient died; Medicare paid the bill). He recounted a troubling story of a 60-year-old late stage Huntington's patient with glioblastoma. “His wife had a very difficult time letting go. We said we could get him back to baseline, but that baseline was late stage Huntington's. They decided to not operate."
What’s more important for neurosurgery, dexterity or knowledge? “We can teach a monkey to do surgery in seven years. Passion is the most important quality. I see senior residents get angry at newer residents because they work shorter hours than they did. They are bitter, and remorseful. Unless you have the passion, you will burn out.” He joked that sometimes beginners can be too passionate. "One of my residents got so excited about a successful shunt [apparently, a common neurosurgery procedure] he performed. It's not that big a deal, we do shunts every damn day. I did not want to burst his bubble so I told him 'Great job!'... Don't tell him I said that!"
How did he cope with such depressing cases? "It is tough. I see cases like Jonathan's every month," he answered. "Everyone manages it differently. For me, as long as I feel like I treated my patient and their family like my family, I sleep fine. It is when I remember at night that I forgot to talk to that family member that it hits me."
A seventy-year-old dermatologist with a strong southern accent held a lunch session to explain why his field is the best: "I cannot think of a single reason why you would not want to do Derm. It pays well. It has unbeatable hours. The patient population is generally quite motivated to get better." He was in private solo practice for much of his career. "Many of my patients, such as lawyers, paid cash." A classmate asked, "Did it get lonely working solo?" He responded, “No, we have nurses.” He described how there are just not many dermatologists, claiming this was the reason why there were so few dermatology residency slots. Dermatology is one of the most competitive residency programs.
Friday was Match Day, a slight misnomer because it is one day after fourth-year medical students hear where they will (or will not) be completing residency. Students and residency programs rank their top choices. Almost 36,000 domestic medical students and international doctors vied for about 29,000 residency slots. Fifty percent of applicants nationwide got their first choice.
The whole school attends the ceremony. Each student goes up to the podium and says something like "I will be will doing Internal Medicine at the University of Southern California." Fifteen percent of the class couples matched. Two individuals need not be married or in the same specialty to couples match. An orthopedic surgeon sent an email out congratulating the class on their impressive Match Day results, but reminded the first through third year students not to slack off. He ended with a quote from Will Rogers: " Even if you are on the right track, you will get run over if you just stand there."
Statistics for the week… Study: 10 hours. Sleep: 7 hours/night; Fun: 2 nights. Example fun: A good friend and former coworker visited for the weekend. We joined Match Day celebration at a pregame followed by a late bar night filled with plenty of Guinness for Saint Patrick's Day. Jane and I saw Beauty and the Beast on Sunday evening.
Anatomy lab was less than 30 minutes: we removed with blunt dissection the posterior muscles around the vertebral column to prepare for next week's laminectomy (removal of the vertebral laminae to expose the spinal cord)! We went over spine anatomy and common spine disorders such as a herniated ("slipped") disk (the gelatinous nucleus pulposus part of the intervertebral disk herniates through the outer fibrocartilage annulus fibrosus) and spondylolisthesis (anterior or posterior displacement of a vertebra). We discussed how aging causes loss of the elastic dampening capabilities of the nucleus pulposus.
Lectures detailed two sensory systems, the anterolateral and medial lemniscal tracts. The anterolateral tract conveys tissue damage (pain), whereas the medial lemniscal tract conveys fine touch and proprioception (vibration and positional awareness). Sensing vibration requires extremely responsive transducer elements in the skin to convert rapid changes in pressure into electrical signals. All these tracts end in the postcentral gyrus in the cerebrum, which forms the sensory homunculus. The medial part receives sensory input from the lower extremity. The genitalia neurons are adjacent to the foot neurons, a potential explanation for why some humans have a foot fetish. The lateral part of the brain receives sensory input from the upper extremities.
Doctor J called the tallest student up to the front. He grabbed a measuring tape and asked the student to step on one end of it. He then measured all the way up his back to the end of his neck -- 5'6. "This is the length of a single neuron in your body." The whole class was amazed. Neurons that sense fine touch and proprioception travel from the big toe up to the spinal cord, ascend the spinal cord in large bundles, and finally synapse in the medulla (part of the brainstem). One cell.
Our patient case: Sherry, a 50-year-old overweight female accountant with uncontrolled diabetes presents to her primary care physician with a foot ulcer. During tax season she is so busy that she forgets to take care of herself. She has not refilled her medications, including metformin, for several months. A neuromuscular exam, specifically using a 256 Hz tuning fork to test for vibration sensitivity, reveals diminished sensory ability in both extremities. She explains that her foot has felt numb for weeks. A cut on the foot went unnoticed, and got infected.
Sherry suffers from diabetic peripheral neuropathy. Uncontrolled glucose levels lead to non-enzymatic glycosylation (adding sugar groups) of proteins,lipids, and nucleic acids. These advanced-glycosylated products (AGEs) interfere with normal function and activate inflammatory pathways. A familiar complication of diabetes is vascular (arteries and veins) damage, which leads to increased risk of atherosclerosis, heart attack, and stroke. This inflammation also damages neurons and their companion Schwann cells (cells that myelinate peripheral nervous system axons). The longest axons are affected first. The neurological deficits such as numbness, loss of pain sensation and balance difficulty start in the foot and travel up the leg. By mid-calf, the sensation loss also begins in the hands. Fifty percent of diabetics have peripheral neuropathy (eighty percent after 15 years). Interestingly, the physician mentioned that twenty percent of prediabetics have some sign of developing nerve damage, suggesting that vibration tests should be used as a screening tool for diabetes.
Sherry had trouble simply walking. As is common among laypeople, classmates associate diabetes with laziness: failure to exercise, overeating. This case prompted us to ask "How could someone exercise if they cannot walk?" The physician concluded, "It is critical for diabetics to check their feet daily. They might not even realize they have a cut or foot ulcer. The infection can spread to the bone requiring hospitalization and, too commonly, amputation." He reminded us that diabetes is the leading cause of amputations [73,000 in 2010]. Sherry described her diabetic foot ulcer, now cured, as a wake-up call. She was discharged from the hospital three months ago and has been taking her medications regularly.
A diagnostic radiologist and an interventional radiologist led a lunch session about their respective specialities. Diagnostic radiologists complete 5 years of training: an internship year typically on general surgery followed by a 4-year radiology residency. Interventional radiologists conventionally would complete a separate 2-year interventional radiology (IR) fellowship, making for a total of 7 years of post-MD training. There are now direct IR residencies that take just 5-6 years.
IR is a subspecialty of radiology. Interventional Radiologists perform minimally-invasive procedures using imaging guidance such as x-ray and ultrasound. These procedures include: central line placement, endovascular (e.g., stents and thrombectomy of blood clots) procedures, radiation treatment, and bile duct obstruction procedures. Other specialities overlap with many of these. Indeed, there is sometimes tension what specialty group performs a given procedure at different health systems. For example, stents can be placed by IR or interventional cardiology; strokes can be treated by neurosurgery or IR.
The interventional radiologist explained why he chose IR: "I loved anatomy. And I like working with my hands doing procedures." The diagnostic radiologist explained why she choose radiology: "I had the worst internal medicine rotation fourth-year. Day after day, I would have a patient die on me. The worst was a 30-year-old cystic fibrosis patient, the exact same age I was. I was so miserable I considered quitting medical school or not completing a residency. A radiologist lived upstairs of me and noticed how miserable I was. He suggested I shadow radiology. Never looked back."
She described radiology as the "experts' expert." Clinicians increasingly rely on imaging procedures as opposed to physical examination skills. "Do not go into radiology if you cannot wield responsibility. You decide if someone in the ED goes to the OR or gets sent home." We learned that radiologists are highly compensated, but also have a higher liability profile: "Every radiologist will be sued several times."
What will the role of machine learning play in radiology? "Computers will not replace radiologists. They will just make radiologists much better at their jobs." The diagnostic radiologist elaborated, "Computer algorithms in some areas are just as good as radiologists in identifying if something is wrong with a patient [high sensitivity]. However, computers are terrible at ruling out issues [low specificity]." I attended a neurosurgery informal dinner where I asked a similar question about radiology. The neurosurgeon was shocked by the radiologist's response, and exclaimed, "Radiologists are terrible at ruling things out. Every report is littered with: 'cannot rule out x, y, or z'. Give me a break, they will be replaced." (See "A.I. Versus M.D.," New Yorker, April 3, 2017.)
I've been working on a personal project in the evenings. My favorite trauma surgeon comes in most Wednesdays at noon to evaluate my progress. She tidies up my dissection then sends me on another mission that our class did not have time to explore during formal anatomy lab. Examples: Find the annular ligament of the radius, the ulnar nerve, or the anterior humeral circumflex arteries. One thing that makes medical school different is that an after-hours project may involve a dead body. In this case, I have a whole cadaver to myself, unlike in anatomy lab where we switch bodies every few months. The cadaver was a black 60-year-old, mildly overweight female. I have developed a deep sense of appreciation for this woman who donated her body so that I could pursue this upper extremity (arms) project focused on nerve and blood vessel anatomy.
One evening around 9:30 pm there was a knock on the locked door. I took off my soaked gloves and opened the door to find the head dean escorting a fundraiser group of dressed-up bankers and business people. They wanted to see the wet lab. I forgot how quickly one adjusts to the sight of cadavers in a formaldehyde-scented room. As I was there by myself, the whole head was uncovered and several chunks of removed fat lay exposed. A few people approached the body, but most were hesitant and stayed at least several feet away. I showed them the nerves and vessels of the arm.
A visitor asked about the purpose of cadavers. I explained that cadavers give unparalleled understanding of human anatomy. Textbooks cannot replicate this experience, especially the geometric relations of anatomical structures. An important part of the learning experience is discovering how the individual died and what diseases he or she lived with. I mentioned that one cadaver had a heart attack, prompting a question from a gentleman in his late 50s regarding what the heart looks like after a heart attack. I explained the cadaver suffered a heart attack in his left anterior descending (LAD) artery, as evidenced by a small, hardened discoloration on the surface of his left ventricle (see previous post). He did not die from the myocardial infarction because hardened scar tissue replaced the infarcted region. If he did die from the MI, the infarcted region would have the same firmness as the rest of the myocardium. The gentleman thanked me, took a peek at the cadaver and left. The next day the dean told me that the wet lab had been the guests' favorite part of the event.
Statistics for the week… Study: 8 hours. Sleep: 6 hours/night; Fun: 1 nights. Example fun: Two classmates and I attended this year's SonoSlam in Orlando, Florida. SonoSlam is an ultrasound competition among medical schools held on a Saturday by the American Institute of Ultrasound in Medicine (AIUM). My favorite part was using the most advanced ultrasound machines. Several of machines were controlled via iPads. One bluetooth-enabled ultrasound probe was only slightly larger than a smartphone and could be controlled via an iPhone app. The competition ended around 6:00 pm. As first-year students without the pathology training of the fourth years, we had low expectations for the competition and we did not exceed them. However, we celebrated our failure with post-competition drinks at a local brewery and "Cutthroat" at a nearby billiards parlor.
In anatomy, we performed a laminectomy. We removed the posterior vertebral structures to reveal the spinal cord, about the diameter of the thumb. We opened up the dura (outer meninges that forms a fibrous protective layer), a continuous white sheath that covers both spinal cord and brain. At each intervertebral level, four roots come off the spinal cord to form bilateral spinal nerves. The ventral root is where all the motor fibers exit the spinal cord to control muscles and glands. The dorsal root is where sensory fibers enter into the spinal cord. Several spinal nerves in the lumbar and cervical regions were surprisingly large, about the diameter of a pinky. How could something the size of a thumb contain nerves that occupied so many pinkies? The answer turns out to be that nerves within the spinal cord are highly myelinated, which maintains conduction speed without the need for a large diameter. Once the neurons fan out from the spinal cord, however, not all of these nerves are myelinated and therefore must be thicker. We also saw the aptly named cauda equina (horse's tail). The spinal cord stops at L4 but the spinal nerves must exit from the lower vertebrae. The spinal nerves flow down the vertebral foramen fibers forming a horse's tail!
This week in lecture we learned about the cerebellum (from the Latin for "little brain") and basal ganglia. The cerebellum is located in the posterior inferior (back/lower) portion of the skull under the occipital lobe and contains an estimated 50 billion neurons in the cerebellum—more than in the entire rest of the brain and spinal cord combined! These cells can be thought of as writing computer programs to determine muscle activity and timing. One program, for example, might determine the sequence of firing hand muscles to grasp a cup. "Anyone who has had one too many cold ones knows what happens when you lose cerebellum function," noted Doctor J. Alcohol affects the the purkinje neurons of the cerebellum first, causing the characteristic drunk stumble.
The cerebellum uses the same neural architecture to process different inputs. For example, whether information is coming from the vestibular (balance) apparatus, or coming from proprioceptive information of the big toe, the information ascends to the densely packed purkinje neurons. The purkinje cells form massive planar dendritic trees that stack together in parallel. Purkinje cells have the same branching pattern as fan coral. Information received from the nervous system is sent along parallel fibers that travel perpendicular to the purkinje dendritic trees, synapsing along the way. This allows an immense amount of connectivity.
Cerebellar lesions, for example from a stroke, are devastating. Simple tasks become near impossible as the victim has difficulty timing an action. We practiced various cerebellar tests including the finger-to-nose test where you ask patients to reach out to your finger and touch their noses. They will have an intention tremor as they near the end of the action. Doctor J commented, "Do not use their nose as the endpoint. A stroke patient will poke his/her eyes out. Use the chin."
We had two lectures on the basal ganglia, cell bodies deep in the brain that are involved in filtering information passing through the thalamus (relay station) to the cerebral cortex. While the cerebellum's outputs dictate the timing of muscle firings, the basal ganglia determine which muscles need to be activated. Lesions of the basal ganglia, for example Parkinson's disease, cause debilitating rest tremors (tremors while not performing an action). We learned that stripes of tape on the floor can help Parkinson's patients with stability. The visual cues of the tape are thought to override the abnormal baseline thalamic input. This simple addition has huge benefits for the patient and caretakers, for example, when the patient tries to get out of bed to the bathroom. "This is an easy way to help keep a Parkinson's patient out of the hospital."
Doctor J brought out a VHS cassette showing various tremors, reflexes, and symptoms of patients with neurological disorders. "It might be old, but it's the best display of these symptoms." It took two IT staff 15 minutes to get it playing. We saw symptoms and movements associated with Parkinson's disease and Huntington's disease. The video was apparently worthwhile; the next day, a classmate shadowing an internist diagnosed a 40-year-old patient with Parkinson's.
Our patient case: Martha, a 62-year-old female with Parkinson's disease accompanied by her daughter Janine. The class quickly fell in love with Martha. She was witty, humble, and kind. Martha was diagnosed about eleven years ago with Parkinson's after presenting with balance issues, difficulty writing, and a rest tremor in her hands. The neurologist explained there are two stages of Parkinson's. "The first stage involves movement and dexterity. Typically two decades after diagnosis, patients enter a second phase characterized by significant cognitive deterioration. There are drugs, for example carbamoyl-levodopa, that are effective at treating the tremor and movement disorders."
Martha explained that it took a while to find the right balance. Too much of these powerful drugs can also cause tremors. She takes her medications every four hours or as needed if the tremors get worse. "If I do not take my medications, I have this terrible slowness," explained Martha. "I want to walk but my feet do not move. They just twitch up and down with the rest of my fidgety body. My body does not respond to my mind."
Asked to describe her typical day and what she wanted others to know about Parkinson's, Martha responded, "Oh, I still do lots of stuff. I cannot drive, but I love to garden and cook. Everything just takes longer for me. Appreciate that it is difficult for me to get to an appointment or brunch at 10:00 am. It takes me several hours with the help of Janine to get ready."
What was her greatest concern? She immediately responded, "That I will become dependent on Janine." She explained that Janine was the only family member who was a significant help. A student asked Janine, "How has this changed your life?" Janine responded, "She is the center of my world. I wouldn't change it. I wish people understood that her disease has not destroyed everything of her. There is a whole life after diagnosis. It doesn't stop there."
Friday afternoon, we practiced motor and reflex tests on each other. Reflexes are elicited by sudden changes in muscle length. Swinging a reflex hammer at a tendon causes a sudden increase in the length of the tendon, which sends this stretch information to reflex centers in the spinal cord. Upper motor neurons communicate with these centers for a net inhibitory effect. Therefore, an upper motor neuron lesion may result in hyper-reflexia (e.g., doctor gets hit in the nose by the patient's foot). As we practiced on each other, two student-examinees shouted, "I got the clonus!" Clonus is when a muscle undergoes a series of involuntary contraction-relaxation cycles after a sudden change in the fiber length. The hospitalist told them not to get too excited about a few beats of clonus: "Wait until you are on the hospital wards."
Seven students stuck around to speak to the physician. One of our classmates had suffered a stroke at age 10. He reluctantly volunteered to have his reflexes tested. We quickly identified hyper-reflexia in his left lower extremity (left leg below the knee). For the patellar reflex (knee), the leg straightened at the knee and then kept going up towards the ceiling. After that we saw more than 5 seconds of sustained clonus. This is entered on a chart as "Grade 4+" (2+ is normal). Further, the physician elicited the "Babinski sign" by moving a pen along the underside ("plantar" surface) of the classmate's foot. His toes fanned out, which is normal for a baby under six months old. After six months, this reflex is typically eliminated as upper motor neurons suppress the primitive response. We thanked our good friend and classmate.
The next day, Doctor J held a group "question and answer" session. The class gets into six-person groups to answer challenging questions. Each group is required to hold up an answer. Doctor J would then delve into why Group 1 picked "C" whereas Group 2 erroneously picked "D". Type-A Anita did not attend stating, "I feel humiliated when I go to these question/answer sessions and he pimps me about why I got the question wrong."
Lunch outside with nine classmates: A woman checked CNN headlines about the missile strike on Syria on her phone and yelled that Trump was a warmonger. Type-A Anita added, "On top of this, Gorsuch was confirmed. We are going back to the Stone Ages." The topic somehow turned to race relations. A classmate chimed in, "Ben Carson got appointed only because he is black." A female classmate from a rural conservative family opined, "America has our class divisions but we are by far the most tolerant country compared to anywhere else." Immediate reactions stormed in. "This is because Western culture portrays whites as heros and blacks as criminals," a female Asian student asserted. "It is the West's fault that other countries are not tolerant because they watch our movies and pop culture." The discussion settled down after someone brought up the livestream of April the Giraffe (a pregnant resident of an animal park in New York).
Statistics for the week… Study: 8 hours. Sleep: 8 hours/night; Fun: 1 night. Example fun: After class, we played soccer with Ph.D. students in the rain followed by burgers and beers.