Medical School 2020: Year 1, Second Half

Medical School 2020: Year 1, Second Half

one section of a Fifth Chance Media book, ISBN 978-1-944861-02-5.

To preserve patient confidentiality, ages and other details are slightly altered. Students and teachers are also pseudonymous. We're now at the beginning of 2017.

Year 1, Week 19

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.

Year 1, Week 20

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).

Year 1, Week 21

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.

Year 1, Week 22

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. Surgeon Sara, an aspiring general 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.

Year 1, Week 23

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.

Year 1, Week 24

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.

Year 1, Week 25

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.

Year 1, Week 26

"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 estrogens, 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.

Year 1, Week 27

"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.

Year 1, Week 28

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.

Year 1, Week 29

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.

Year 1, Week 30

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.

Year 1, Week 31

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.

Year 1, Week 32

Eye week started off with a two-hour dissection of the orbit (cavity of the eyeball). We used bone chisels to open the orbit and remove an eyeball by cutting the various ligaments and nerves anchoring it to the skull and brain. A human eyeball feels squishy but not delicate.

The eye comprises several layers: eyelid, cornea/sclera, iris, lens, retina, sclera (again). The eye lids contain conjunctiva epithelia which is continuous with the white outer sclera of the eyeball. The sclera is a white, fibrous connective tissue. The sclera merges with the cornea, a thin transparent convex protrusion that provides much of the optic refractive index of the eye. Behind the cornea is a cavity filled with aqueous humor, a watery secretion. The iris (colored portion of eye) is actually a muscle with radial and circular fibers that control the size of the pupil. The pupil is literally a hole in front of the lens. Light hits the cornea, enters the anterior (front) chamber, traverses through the pupil into the posterior chamber, and hits the lens to be focused on the retina, which is at the back of the vitreous chamber. Classmates, including myself, tended to hear the term "posterior chamber" (in front of the lens) and erroneously identify the much larger vitreous chamber (behind the lens).

Most of my anatomy group left early, but one classmate and I stayed to open the eyeball. We cut open the sclera with a scalpel and held the lens in our hands. It felt like a marble with an opaque yellowish tint. Several cadavers had artificial lenses, which felt surprisingly similar. The vitreous humor, inside the vitreous chamber, felt gelatinous. The retina looked like a white transparent sheet, except for a small protrusion on the medial aspect (closer to the nose) of the retina. This was the optic disk, where nerve fibers merge to exit the eye and the retinal artery enters the eye to supply the retinal layers with blood. The retina peeled off with forceps. We put the eye back together and placed it back in the orbit.

The retina, except at the optic disk, contains photosensitive compounds that transduce light into electrical signals. Rods, cells with the pigment rhodopsin, are sensitive to small amounts of light (as small as a single photon) and line most of the retina. Cones, cells with different photopigments excite depending on the specific wavelength (color), require larger amounts of delivered energy to activate. The density of photosensitive cells increase in an area of the macula with the highest density of cones in the fovea. Rods are important for night vision, while cones enable us to see color and detail.

A student asked, "What is the resolution of the eye?" Doctor J said this is hard to define. Each eye has 150 million photosensitive cells (rods and cones) [compare to 100 megapixels for the highest-resolution cameras circa 2017]. These signals converge onto 1.2 million ganglion cells that transmit the information via the optic nerve to the brain. Most of these ganglion cells originate from the fovea, a region the size of 1.5 mm. Image details are integrated by the primary visual cortex and visual association cortex. If you're looking for something small at night, try scanning with your peripheral vision because the density of rods is higher outside of the fovea.

Our eyes have six extraocular muscles that provide the extraordinary range of motion of the eye. To support binocular vision and depth perception, the eyes have elaborate mechanisms to maintain foveation through the horizontal and vertical gaze centers in the brainstem. Strabismus ("cross eye") is a misalignment of each eye causing an image to hit different parts of each retina. Strabismus causes diplopia (seeing double). Compression of one of the nerves that innervates these extraocular muscles can lead to diplopia when they gaze a certain direction.

Our patient case: George, 74-year-old white male with hypertension and hypercholesterolemia presents for blurry vision. An eye exam reveals intact extraocular muscles with decreased visual acuity. Inspection of the macula with an ophthalmoscope reveals the characteristic geometry of drusen (lipid deposits in the choroid vascular region deep to the photopigment layer).He is immediately referred to an ophthalmologist for Age-associated Macular Degeneration (AMD).

[AMD is the leading cause of vision loss for individuals, with white Americans being at high risk starting around age 65. Fifteen percent of white Americans over age 80 have AMD (https://nei.nih.gov/eyedata/amd). Type-A Anita muttered "white privilege" when we went over a clinical trial of a drug to treat AMD. Reflecting the higher prevalence among whites, the study had 93-percent white enrollment.]

The ophthalmologist performed an Optical Coherence Tomography (OCT), shooting low energy light (infrared) into George's retina to create beautiful micron-resolution images of the retinal layers. The study revealed detachment of the macula due to wet AMD. The choroid plexus (blood vessels on the exterior of the retina that supplies the pigmented cells) began to grow into the photopigment layers causing microhemorrhages. George was fortunate to get this diagnosed before his whole macula became detached.

Every six weeks, George goes to his ophthalmologist for a shot of Bevacizumab (Avastin), which contains antibodies against vascular endothelial growth factor (VEGF). This drug is injected into his vitreous chamber to prevent the growth of the invading blood vessels. "These drugs have saved my vision. I am able to drive, read, really do everything I want to do." George was going in this week to get his shot before departing on a cruise next week.

"VEGF treatment has really been a godsend," explained the ophthalmologist. "It prolongs patients' vision for years. For the unfortunate few who do not respond, there are some other options." One was a telescope implant to replace the lens with a magnifying telescope that focuses an image on a different part of the macula that is healthy. Students dubbed this "going bionic". A more drastic treatment option is macular rotation. Surgeons detach the retina and rotate is to have a new, more healthy vascular choroid plexus.

A student asked about the difference between Avastin, originally developed as a treatment for colon cancer, and Lucentis. Lucentis, FDA-approved to treat wet AMD, is a cleaved form of the anti-VEGF monoclonal antibody Avastin, at roughly 1/40th of the dosage used for colon cancer patients. Lucentis may be able to penetrate deeper into the retinal layers because of the antibody's lower molecular weight. Lucentis costs $2,000 per dose, whereas the amount of Avastin necessary for wet AMD therapy costs $50. The ophthalmologist explained he always starts with off-label Avastin. "I have only anecdotal evidence that a few of my patients respond better to Lucentis." [This makes sense given that the drugs are essentially chemically identical.] Genentech makes both Avastin and Lucentis. "Why would the company fund a multi-million dollar trial to approve a drug that costs less?" If all Medicare patients were prescribed Avastin instead of Lucentis, Medicare Part B is estimated to save $18 billion and patients save nearly $5 billion over a 10-year period (http://content.healthaffairs.org/content/33/6/931.abstract).

That evening, I spoke with some fourth-year medical students going into surgery about the match process. I learned that many general surgery ("Gen Surg") residencies are trending towards the "5 + 2" option. Gen Surg residencies had typically been five years. After residency, you could then get a job, or apply to a 1-2 year fellowship (e.g., cardiothoracic, vascular, etc.). In order to make graduates more competitive when applying for fellowships, some prestigious surgery residencies are now requiring two years of research in the middle, hoping that the publication record will appeal to fellowship admissions committees. Thus what had been 4 years of medical school, plus 5 years of residency, plus up to 2 years of fellowship (11 years) might now turn into a 13-year training process.

An attending repeated his wish (see Week 8) that regulations would allow him to teach us more. "LCME caps the number of formal class hours at about 26-28. There just isn't enough time to do extra projects, especially if they do not advance LCME-designated areas." He told administration that he would even volunteer his time for optional events. "Administration responded by saying, 'Students would complain that they feel obligated to go…' Don't we have capitalism? Instead of stooping to the lowest denominator, you work harder, get better, and make more money."

At lunch, Type-A Anita lamented the loss of Obama. Several students agreed, but added, "Trump's election is actually a blessing. Now we have unprecedented activism against racism and sexism. In the long run this will be good." Type-A Anita agreed, "But honestly, if we blow up the world?" They ended by saying how much they missed Obama's dogs and looking at a Pinterest account of Merkel Faces.

Statistics for the week… Study: 10 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Afternoon drinks at recently opened brewery. There must be six new breweries planning to open by the end of the year.

Year 1, Week 33

Auditory week began at 8:00 am with some classmates upset because the room was different than stated on the shared Google Calendar that is our primary source of scheduling information: "Ugh, now I have to pack all my things up." We moved across the hall and Doctor J tried to reassure the class by promising it wouldn't happen again.

The ear is involved in hearing and balance. The pinna (outer ear flap, also called auricle) funnels sound into the ear canal to strike the tympanic membrane. On the other side of the tympanic membrane is the middle ear, an air-filled cavity that is connected to the oral cavity through the eustachian tube. We practiced using otoscopes on each other in a clinical workshop led by a female otolaryngologist in her 40s. It hurt! Every few minutes we would hear a shrieking "ouch". The worst was when a student from one group hastily grabbed a new tip to practice the technique lurched over and hit another group's otoscope wielder. The otoscope twisted in the student's ear. Despite these mishaps, we learned a great deal. After you get past the ear wax and hair, the tympanic membrane comes into view. The malleus, one of the three ossicles (ear bones), is attached at the umbo, a small white spot near the center of the tympanic membrane. In a normal ear you can see the pale outline of the malleus through the transparent membrane.

The otolaryngologist went over some commonly diagnosed ailments using the otoscope. A more opaque tympanic membrane suggests fluid, instead of air, is behind the tympanic membrane in the middle-ear. The fluid is typically from a middle-ear infection, which can cause temporary hearing loss and pain. She explained that we can also diagnose pierced ear drums and grossly malformed ossicles. A student asked, "What are the common procedures you do?" The answer was removing the broken ends of Q-tips from the ear canal. He followed up with "Do ENTs promote the use of Q-tips for business reasons?" She laughed and responded, "Oh, God, no! Those visits are so boring." Her passion is performing cochlear implants to restore hearing in children (see below).

When a sound wave hits the tympanic membrane, the membrane transmits the vibration to the the ossicles. The malleus ("hammer") rotates the incus ("anvil"), which in turn displaces the stapes ("stirrup"). The stapes is the interface between the middle ear and the cochlea, a fluid-filled, snail-shaped bone of the inner ear. The stapes lies in the oval window, described as a "bony defect" of the inner ear, that interfaces the stapes with the encapsulated fluid (note that if you didn't have this "defect" you wouldn't be able to hear). The stapes transmits the mechanical energy to propagate a pressure wave through the tube to the exit at the round window (a "bony defect" of the inner ear interfacing with the air-filled middle ear). The cochlea is U-shaped, with the oval window opening into the scala vestibuli. The 360-degree turn is called the heliotrema, and the scala tympani ends at the round window.

The two divisions of the tube (scala tympani and scala vestibuli) are separated by a space, the scala media, another fluid-filled tube. This turns out to be the actual source of all hearing sensation. The scala media changes in thickness along the length of the tube, making it sensitive to different sound frequencies. For example, one frequency might lead to a high pressure in the scala vestibuli 1 mm from the oval window, and a low pressure in the scala tympani 1 mm from the round window. This signal would cause the scala media at this region to bend towards the scala tympani. Along the length of the scala media are hair cells, receptors that excite neurons when the scala media deforms as little as a few nanometers. The sensation of sound occurs when signals travel through the brain stem into the primary auditory cortex, part of the surface of the brain that happens to be near the ears. A cochlear implant works by turning the varying voltage from a microphone into nerve signals corresponding to what would have been the movements of the hair cells.

As will become important in the patient case below, the scala media is continuous with another fluid-filled bone, the vestibular apparatus, an accelerometer critical for balance. This tube is divided into three thin canals (sensing rotation) and two sacs (sensing linear acceleration). Due to inertia, the fluid inside the tube will tend to stay put as the head moves, enabling hair cells to sense a change in pressure within any of the five compartments.

I ate lunch outside with Straight-Shooter Sally. She is the first person in her family to go to college, let alone medical school. Her father is a mechanic. She worked for three years after college as a social worker with adolescent drug addicts in a poor urban neighborhood. "These kids quickly get involved with the drug scene," explained Sally, "Drugs are the easiest avenue to create friend groups and to avoid attack by the gangs. When kids get arrested they are given the option of going to juvy or rehab. Everyone choses rehab." Does rehab work? "Every summer I would come back and see the same kids. It was a revolving door and we did not have any tools to make a difference. The three-month rehab was nothing for them. Their father went to jail for three years—what's rehab speaking to a counselor for a few months?" She continued, "These kids go to failing schools, come home to disorganized families, and the only thing they aspire to is what they see in the community. The drug dealers are the ones who have the snazzy cars, women, and money." She concluded, "I don't know the answer, but these kids need help—education, role-models, jobs, anything. Counseling was not going to solve it. I had to get out of there." She switched jobs and became a health coordinator before starting medical school at age 28.

Our patient case: Giorgio, a 50-year-old salesman who developed right ear pressure and diminished hearing after an evening shower. When he woke up, his ear felt like it was about to "pop" and he had lost all hearing on that side. Two common tests with tuning forks, the Rhine and Weber tests, suggested that the hearing loss was due to a sensory-neuronal deficit rather than a conduction deficit. In other words, he had damage to the hair cells, cochlear nerve, or brain cortex, rather than a mechanical blocked ear or perforated tympanic membrane. An MRI revealed an acoustic schwannoma, a non-malignant tumor of the supporting Schwann cells of the vestibulocochlear nerve as it exits the internal acoustic meatus into the cranial cavity. The tumor had begun to squeeze the cochlear nerve. "Most acoustic schwannomas grow less than one millimeter per year," said the neurologist. "Some years they just lay dormant. For whatever reason, they might spike for a few months then go back into a dormant state." Georgio's tumor was removed by a surgical resection through a retrosigmoid craniotomy approach (incision behind the ear).

The neurosurgeon (not Giorgio's surgeon) explained the risks. "It all depends if the tumor has facial nerve involvement." The facial nerve exits the cranial cavity in the same hole, the internal acoustic meatus, as the vestibulocochlear nerve. If you touch these fibers, it can lead to ipsilateral facial paralysis." During the surgery they insert electrodes into the facial nerve to verify, after each layer of tumor is removed, normal conduction from the surgical site to the facial muscles. "There is not a consensus on whether the whole tumor should be removed if there is facial nerve involvement. If you can get, say, eighty percent of the tumor, you might be able to resolve the hearing deficients and decrease the risk of facial nerve damage. But, the tumor could slowly grow back." My classmates and I watched a Youtube video on the surgery (https://www.youtube.com/watch?v=PBE5rQ7B0Ls). "This is wild," exclaimed an aspiring female surgeon.

Giorgio underwent a full resection. He quickly regained most of his hearing. "I have worse hearing in my right ear, especially in the higher frequencies. For the most part, I hear fine." He does have persistent tinnitus (ear ringing). "Right now, focusing on it, I hear it, but I get used to it." He experienced terrible balance issues for months after the surgery. "I had to completely relearn how to walk. My whole balance seemed to have just reset to a new normal. I was completely dependent of my family for three months."  He also experienced a poorly healing wound on the skull behind the ear. "I was taking airline trips for my job with an open wound on my head. Not the most sanitary environment. One day in the car, my wife looked at my wound, and forced me to go see a plastic surgeon." The plastic surgeon performed a skin graft to revascularize the infected wound. The wound healed shortly thereafter. The neurosurgeon added, "I see these occasionally. It's not a petrid, ozzy infection. It's a lingering infection." Despite this complication, Giorgio was very satisfied with his care. He is slowly getting back into playing competitive tennis, although he still experiences balance issues.

We learned that Giorgio immigrated to the US as a student. He still maintains citizenship from his Scandinavian birthplace. A classmate asked what kind of treatment he would have received under the socialized medicine system of his birth country. "Completely differently," explained Giorgio. "I would not have been allowed to get operated on. If it is not considered life-threatening or malignant they would not pay for it." One classmate, a Canadian citizen and US green card holder joked, "I keep my Canadian citizenship for a Get Out of Jail Free card. If I get cancer, I'm packing my bags and heading to Canada."

I shadowed my physician mentor for an afternoon. It was a busy day so he saw some patients without my assistance. In 4 hours, I saw 7 of the 14 patients. The first patient was a 45-year-old gentleman, overweight but certainly not obese, presenting for follow-up after hospitalization with a transmetatarsal amputation (TMA). He was in disbelief after losing half of his left foot (including the toes) due to a foot ulcer. The physician delved into how he was managing his diabetes. His last sugar readings were off the chart and from over a year ago. He had not been taking his medications for several months. "It was too expensive," he explained. This was typical of our patients who make too much money to qualify for Medicaid, but not enough to afford Obamacare health insurance. Our patient's motivation: "I will do anything you tell me. Just let me have two legs when I see my thirteen-year-old son graduate college."

The next patient was a thirty-year-old mother presenting for follow-up for a prescription opioid refill indicated for joint pain. We informed her that the state has a new law requiring an annual recreational drug test for prescription opioid recipients. She responded, "Yeah, I smoke weed." She will come back in six weeks for her drug screen. The physician told me that this doesn't always work out: "One of my patients failed the drug test for marijuana. I gave him a second chance six weeks later. He remarkably tested clean for weed… but positive for cocaine." He did not get the refill. My attending also mentioned that these new rules will be costly for patients. "Insurance companies generally do not pay for drug screening. Patients have to pay $200 out-of-pocket unless they're on Medicaid."

The next two patients, a 40-year-old man and a 70-year-old woman, both presented for follow-up due to chronic obstructive pulmonary disease (COPD). Both smoked a pack a day. The doctor told each, "If you keep this up, you will eventually be on oxygen." Both had no desire to quit. COPD patients have this terrible sensation of not being able to get a full breath. Most of the COPD patients I have seen are 60 or older. They figure that they are beyond the point where quitting will help. But this forty-year-old male who could not even walk up his driveway without an inhaler! I remembered on the drive to the office I heard the daily radio ad for an oxygen machine cleaning apparatus.

A gentleman in his late fifties presented for follow-up after an ED visit. He was accompanied by his daughter. His whole face was bruised, with a large lesion on his brow. He had a stiff neck. I went in first to interview him. What happened to you, sir? "I asked my neighbor to get his dog under control. The crackhead punched me in the face. I punched him right back. He has it much worse than me." No charges were pressed. We changed his bandages, and refilled some of his prescriptions.

A female in her thirties presented for epigastric pain. I interviewed her first and performed an abdominal exam. Tenderness was noted in her mid-epigastric region (above the belly-button). She had been taking lots of advil (NSAID) for lower back pain. NSAIDs block production of prostaglandins, an inflammatory signaling molecule, which are needed  Prostaglandins are needed in the stomach to produce mucous. Prolonged use can lead to severe stomach ulcers as the acid and stomach enzymes interact with the epithelial lining of the stomach. I could not rule out pancreatitis. This was one of the first cases where I could imagine the flow of the interview. It was exciting asking questions to rule out various hypothesizes on the differential. The experience highlighted the differences between diagnosticians and procedural work. We prescribed her omeprazole and told her to use tylenol, if needed, instead of ibuprofen. "If the pain doesn't get better, we'll have to get an ultrasound or scope. I can't rule out pancreatitis but it is probably just gastric ulcers."

The next patient was a construction worker in his late thirties presenting for a painful bump on his thumb. "I can barely work." The physician thought it was a gangrene cyst. He usually would drain it himself, but it was on a precarious location of the interphalangeal joint. We referred him to a hand specialist. He was hopeful he would be able to get an appointment before he wielded another jack-hammer.

The last patient at 5:00 pm, a male patient in his thirties, had trouble hearing in one ear. Examination with the otoscope revealed a waxy ear canal. The nurse and I used used an ear lavage with warm water and hydrogen peroxide to remove large chunks of wax. It took about 30 minutes.

The next day, a classmate and I discussed the construction worker's prospects of getting an early appointment with the hand specialist. He described how the earliest appointment with his primary care doctor was in a week and half. At the appointment, despite having seen this classmate on three previous occasions, the doctor had no idea who he was. After shadowing physicians for a few months, we had no trouble understanding this interaction. Doctors have to see enough patients to generate target RVUs (relative value units) and at the same time have to grapple with clumsy electronic medical record (EMR) systems. The already-limited time between patients is spent at a PC documenting the encounter. There is no time to review the next patient's chart. My physician mentor (in his 40s) says "the medical system is failing your generation."

Is there hope on the horizon? My mentor is able to save some time with the EMR by using dictation software, which "has improved remarkably in just a few years." The classmate whose wife is in physician assistant (PA) school said, "People talk about there being a physician shortage. I disagree. I think there is a huge physician surplus and not enough ACPs."  [ACP is an "advanced care practitioner," e.g., a nurse-practitioner or physician assistant]. He continued, "Ninety-five percent of cases could be managed with training consistent with ACPs; when they do not have enough training, they bring in the supervising M.D.. M.D.s should become more research-focused. I hate research so I am not sure why I am doing the M.D. route." PAs do not complete a residency after school; instead, they get a job paid much more than a resident salary. Further, PAs are able to switch specialities whenever they want.

Statistics for the week… Study: 12 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: A classmate’s mid-20s roommate is an accountant for the hospital. He has become a regular at our class outings, although he has not become involved with any female classmate to my knowledge. We threw a party for the post-tax season celebration where several PA and nursing students attended.

Year 1, Week 34

One of the first slides for the three hour-long lectures on higher cortical function involved an updated Gallz’s phrenology for 21st century tasks (https://blakerivers.files.wordpress.com/2010/06/male-female-brain.jpg). Tattooed Talia, sitting next to me, expressed outrage: "Shopping! Jealousy!" During a break, Pinterest Penelope, a female classmate and social chair whose laptop screen is often filled by Amazon or Pinterest during lecture, said to Talia, “I love your boots! Where did you get them?” Talia and Penelope spent the rest of the break discussing the challenges of ordering the right shoe size online.

A psychiatrist in his 50s came in to present research on schizophrenia. Schizophrenia runs in families. According to the NIMH, "The illness occurs in less than 1 percent of the general population, but it occurs in 10 percent of people who have a first-degree relative with the disorder, such as a parent, brother, or sister." According to the latest research, a region of the prefrontal cortex (surface area of the brain) is less metabolically active in individuals with schizophrenia. Unfortunately, nobody knows whether this is a cause or effect of schizophrenia. Nonetheless, the psychiatrist suggested screening individuals at risk of schizophrenia with fMRI(functional Magnetic Resonance Imaging) to measure prefrontal cortex activity. If below normal, preventative interventions could be attempted.

After lecture, the psychiatrist talked about his interest in the mental health of incarcerated individuals. "Society is committing genocide against these prisoners, primarily blacks. They develop terrible mental illnesses in childhood. When they become incarcerated these illnesses spiral out of control. It is a sick cycle." He was lobbying state legislature for more extensive mental health programs in state jails. He also talked why he loves psychiatry. "It is a surreal experience to witness some of these disorders. Bipolar disorder causes patients to swing between fits of mania and extreme depression. We can predict these cycles with almost pinpoint accuracy."

We had two hour-long lectures on cerebral blood regulation. The brain always needs 750mL of oxygenated, glucose-rich blood per minute. That's 15 percent of resting cardiac output, which totals roughly 5L per minute. When you begin to exercise, stroke volume and heart rate increase causing a surge in cardiac output to about 12L per minute. How does the brain maintain constant perfusion (blood supply to tissues) while cardiac output varies? The increased pressure is sensed by stretch receptors in arteriole walls of the brain. The increased wall tension causes the arteriole smooth muscle to constrict to relieve this increased wall tension. This myogenic (muscle) response increases the vascular resistance of the brain tissue, thus maintaining the 750mL-per-minute perfusion, and diverting flow to other areas of lower resistance, for example, muscle. The opposite occurs when there is a decreased cardiac output from, from example, hypovolemic shock or cardiac insufficiency.

The two lectures that followed detailed anatomy of cerebral blood supply. The blood supply to the brain originates from the carotid arteries and the vertebral arteries. These form a miraculous structure at the base of the brain called the Circle of Willis. If one contributory artery is blocked, the brain will still get plenty of flow from the others. Doc J commented, “Evolution clearly valued ensuring the brain gets its oxygen and glucose.” The Circle of Willis feeds the six bilateral (left/right) arteries of the brain: left/right anterior cerebral artery (ACA), left/right middle cerebral artery (MCA) and left/right posterior cerebral arteries (PCA). The MCAs supply most of the brain. Unlike other tissues such as muscles, the brain does not have any energy reserves. Without a continuous supply of glucose (or ketones in the fasting state) and oxygen, brain tissue begins to die within minutes. A classmate and his girlfriend are passionate about fitness and supplements. They fast for three days every two months to "reset the system". He thinks a brain diet of ketones will help prevent Alzheimer's Disease.

Anatomy lab investigated the contours of the cranial cavity and the main blood structures. Due to time constraints, the instructors decided to perform the time-consuming removal of the brains from our cadavers' skulls. Next week we will explore "brains in buckets". Some students were disappointed. "I've been looking forward all year to removing the brain." One of our favorite labs was during the heart unit. We were simply asked to "remove the heart". A student commented how he found removing the structures that anchors the organ of interest helps build understanding of the anatomic relationships.

With the brains removed, we saw the holes (termed foramina and fissures) in the cranial cavity through which structures such as nerves and blood vessels pass. There are 12 holes per side that we need to know, e.g., foramen magnum (for the spinal cord), superior orbital fissure (optic nerve and ophthalmic artery), foramen rotundum (sensation of the face), and the hypoglossal foramen (nerve to tongue muscles). About half the cadavers still had their Circle of Willis. It looks more like a pentagon. You quickly appreciate how anatomic variations can lead to immense clinical differences for the exact same stroke. Some cadavers have more developed connections within the Circle of Willis (posterior communicating arteries and anterior communicating artery). These individuals would have a less severe stroke with an occluded carotid artery.

My favorite trauma surgeon discussed the two different types of strokes. An embolic stroke is caused by a decrease in blood perfusion to a part of the brain. This is commonly caused by a blood clot traveling up to an artery of the brain or from the slow accumulation of plaque causing stenosis (narrowing) of an artery that supplies the brain. A hemorrhagic stroke is caused by blood leaking out from a vessel, typically from a ruptured aneurysm or prolonged hypertension causing small tears in a capillary bed. We viewed different MRI and CT scans of strokes. She described the "Death-Star" sign. A subarachnoid hemorrhage ("sudden worst headache of your life") in the Circle of Willis leads to a five-pointed star on CT scan as the blood pools in the contours of the cranial cavity.

A first-year vascular surgeon fellow attended the dissection. He described the carotid endarterectomy, a procedure to treat Atherosclerosis (hardening and narrowing of arteries) and thereby reduce the risk of stroke. The common carotid artery bifurcates into an external and internal carotid artery typically a few centimeters above the thyroid cartilage at a bone called the hyoid bone. The turbulent flow at this bifurcation makes this a high risk site for plaque build-up and intimal (innermost layer of blood vessel) thickening causing stenosis (narrowing) of the internal carotid. The increased blood velocity and shear stress on the plaque wall increase the chance that a small calcium deposit will chip off. As this silent killer travels from the large diameter carotid to smaller arteries, the small deposit begins to enlarge as the body’s clotting system takes over. This blood clot can then get lodged in a small artery. If it gets lodged in the ophthalmic artery, for example, it would causing sudden “curtains to fall” as the retina becomes starved. If it occludes part of the middle cerebral artery, it might cause weakness of the upper extremity and face.

Carotid plaque can decrease overall perfusion pressure to the brain. The Circle of Willis can maintain normal cerebral perfusion pressure with 85 percent stenosis of single internal carotid artery. Above 85 percent, the brain tissue supplied by the end of the main arteries begin to get less flow, leading to a "watershed infarct" with slurred speech and poor comprehension of words.

The carotid endarterectomy is analogous to snaking out a slow bathtub drain. The vascular surgeon detailed the steps while making cuts into a cadaver. He made an incision along the neck exposing the sternocleidomastoid muscle (SCM). The SCM was retracted to reveal the carotid sheath. He opened the carotid sheath and retracted the internal jugular vein and vagus nerve before clamping the carotid arter. In a live patient, he would then have measured the back-flow pressure distal to the clamp. "I need to ensure there is enough perfusion from the Circle of Willis to maintain perfusion of the entire brain without one carotid artery. If the pressure is below about 40 mmHg, I need to create a shunt [install a bypass] of this clamped flow." He then opened the carotid artery and scraped away some plaque. He gave us the opportunity to feel the vessel. The cadaver's carotid artery had severe stenosis (greater than 85 percent). The plaque, hard due to the calcium deposits, comes off in sheets. Over half the thickness of the artery was plaque! He then sutured together the carotid vessel incision and closed the wound.

What's the biggest risk of this stroke-prevention surgery? Postoperative stroke. "It's impossible to get all the plaque because it goes all along the vessel. You have to decide where to stop." The surgeon described how he has to ensure that the interior of the artery is smooth. Otherwise these plaque edges will stick out and become dislodged from the shear stress of the blood flow.

The vascular surgeon urged us to follow our interests: "I am still in disbelief I get up every morning and get to perform what I love. It’s just crazy to think about. There is nothing like surgery. Don’t let the amount of time for training turn you off of surgery or any other speciality. Follow your passion." (Fortunately we're all in medical school, so the economic consequences of this advice are not as potentially disastrous as following our passion for painting or poetry.)

Our patient case: Jerry, a fit 42-year-old male presenting to the ED for upper extremity weakness and slurred speech. Jerry noticed he had trouble holding his toothbrush before bed. "When I grabbed the cup of mouthwash, I dropped it. I thought to myself, 'Huh? This is weird.'" I forgot about it and went to bed. When I woke up, my wife said that I was slurring my words. She rushed me to the hospital where everything went black.

Jerry was having a stroke in his MCA. His wife described how furious she was with the doctors. "It seemed like they were just sitting around twiddling their thumbs." The neurologist added, "Because we did not know when the stroke really set in, we could not use TPA. [Tissue plasminogen activator is a potent clot buster.] Guidelines state that unless you can identify the occlusion occurred within an hour, TPA administration could cause hemorrhagic stroke causing more harm than good." [A recent article in NEJM recently disputes this time restriction. (http://www.nejm.org/doi/full/10.1056/NEJM199512143332401#t=article).]

Jerry had a relatively minor stroke in a small branch of the left MCA. It still took months to recover from it. He had trouble with his right arms, swallowing and speaking. "I could barely speak for three weeks." He went to occupational therapy for two months. Most people would now have a hard time realizing Jerry had a stroke. "The main issue I have is that I cannot feel my entire right chest, shoulder and upper back. Some words seem to have just left me. I cannot seem to recall a lot of complicated words."

"What scares me the most is why this happened. I am a pretty fit person." The neurologist explained that the Jerry does not have the main risk factors for a stroke. "He does not smoke, does not have afib [atrial fibrillation]. We could not even find an ASD [atrial-septal defect]." He brought up the ASCVD risk estimator to show he was doing pretty well (http://tools.acc.org/ascvd-risk-estimator/). This nagged at Jerry. "I did not know what to tell my two kids." The neurologist recommended he join a clinical trial with a new drug to prevent strokes. "This clinical trial has given me confidence, even though I don't know if I am on the drug or the placebo. I just believe it is doing something." After one year, Jerry will know to which group he had been assigned and, regardless of his original group, will have the option to be on the new drug.

Type-A Anita is soliciting $12,000 in donations on KickStarter for a “historic photo book”. This will contain Anita's, and others', photos of protests over the first one hundred days of President Trump. Her Facebook post request contributions from friends and family: "Thank you & Keep Marching!" She has $2,200 pledged.

Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Jane and I took a break from studying and took a boat around a nearby lake with her family. George, a classmate in his late 20s, got engaged over the weekend during a beach getaway. I commented on their Facebook post: "Congrats, Julie, I cannot wait for you to move to here!" This created havoc. Julie, a marriage counselor, had not told her boss that she was moving. She frantically told George to delete the post.

Year 1 Week 35

Three hour-long lectures on child development. A student commented, "Who knew that children are blind as a bat when they are born. 20/300 vision!" Afterwards, several instructors brought in children aged one month to five years for a workshop. Each pediatrician noted specific tasks, behaviors and skills. Dorothy Disinterested was reprimanded for "not being interested in the subject material and being on her cellphone". Dorothy explained afterwards, "I am just not interested in children."

Also three hour-long lectures on cerebrospinal fluid (CSF) circulation. The brain is surrounded by an outer connective tissue called the meninges (meningitis is the inflammation of this connective tissue) composed of three layers (outer to inner): dura, arachnoid, and pia. The dura, a fibrous white sheet, is strongly adhered to the inside of the skull and, via dura folds, divides the cranial cavity into quadrants. The falx cerebri divides the brain into left and right hemispheres. The tentorium cerebelli is a horizontal sheet that separates the cerebrum (above) from the cerebellum (below).  These dural folds are tightly adhered to the arachnoid, named for its resemblance to a spider web, a clear membrane that wraps around the exterior surface of the brain. The innermost layer is the pia, another thin membrane, follows the contours of the brain into its crevices (sulci and fissures). The subarachnoid space, the space between the arachnoid covering and the tightly adhered pia, is filled with CSF.

CSF is produced in four connected brain cavities called ventricles. The left and right lateral ventricles connect to the third ventricle through a thin constriction called the interventricular foramen of Monro. The third ventricle drains through a narrow constriction called the Aqueduct of Sylvius into the fourth ventricle of the brainstem. CSF exits the fourth ventricle into the subarachnoid space through three foramina (the two lateral Foramina of Luschka and the medial foramen of Magendie). Students appreciated that the early 19th-century anatomists who discovered these respective structures have last names whose first letters correspond to the structures' anatomical positions: Francois Magendie for medial; Hubert von Luschka for lateral.

The CSF suspends the brain in fluid, thereby protecting the delicate tissue structure from small shocks and providing a buoyancy effect, which turns a 1500-gram brain into 25 grams. Without the buoyancy effect, the weight of the brain would crush itself. Each ventricle contains a choroid plexus where 500mL CSF, enough for four complete daily changes, is produced by ependymal cells. CSF circulates through the ventricles, draining metabolic waste products of neurological activity, such as glutamate (excitatory neurotransmitter) and potassium, into the subarachnoid space.

My favorite trauma surgeon explained the different types of hemorrhages. Blunt trauma can fracture the skull causing an epidural hemorrhage, rupture of the meningeal arteries that travel along the inside surface skull. After a car crash, the patient will go unconscious. They will then wake up for a "lucid interval" of roughly 30 minutes, then suddenly go unconscious again as the ruptured meningeal artery leaks into the brain. A subdural hemorrhage typically occurs in old age. The brain shrinks, which stretches the small veins that drain blood from the brain to the large venous sinuses in the dura. Slight trauma can then cause the veins to rupture, starting a slow bleed that brings the patient into the ED days or weeks later with headache and confusion. Both types of hemorrhages can result in sufficient elevation of pressure to cause herniation of the brain, in which parts of the cortex protrude through holes in the skull.

Our patient case: Greg, a 23-year-old male with Mike, his cardiologist father and Jennifer, his nurse mother. Jennifer's pregnancy was completely normal until a 30-week ultrasound. The obstetrician noted an enlarged skull with a protrusion on the right side. The mother explained, "My OB told me, 'Something came up on the ultrasound that we need to take another look at.' I knew something was wrong. Whenever a physician sees something bad that they have to refer you out to a specialist, they refuse to tell you a definitive answer.." Jennifer waited several hours in the waiting room until the specialist could see her. "I did not want to call Mike because he was dealing with a tough heart case."

Further ultrasound examination confirmed that Greg's Aqueduct of Sylvius had narrowed, causing hydrocephalus (abnormal accumulation of CSF). The choroid plexus continues to produce CSF despite the increasing ventricular pressure in his lateral and third ventricles. The increased ventricular pressure and size was damaging developing brain tissue and preventing the skull from closing. The physicians told Mike and Jennifer that Greg would unlikely be able to survive and that, if he did, he would have severe cognitive deficits.

"We knew this was bad," continued Jennifer. "We both have medical backgrounds so we were imagining the worse. Mike immediately became an expert on this condition. Keep in mind in those days Google was not around. Mike went to medical libraries to scour the limited literature on this condition and its outcomes. Our doctors recommended we terminate the pregnancy. But when I saw the ultrasound, I could not terminate. He was my boy." Jennifer was immediately scheduled for a cesarean section. Greg was whisked away to the NICU for intensive treatment. He had a ventriculoperitoneal shunt (tube inserted through brain tissue into a ventricle to drain CSF into the peritoneal cavity) and several cranial skull surgeries to release the increased intracranial pressure.

Greg is 5'5 with a cheerful smile. He speaks slowly but carefully. "More articulate than some of our classmates," commented one student afterwards. He chuckles after his jokes. He has terrible vision as a consequence of visual cortex damage.

Most of Greg's medical care occurred in his infancy. He had two additional surgeries to restructure his skull at age 8 and 14.  He lives with his parents and works part-time as a clerk at a local grocery store. His mother said that Greg's social life is more active than their own: "There are all these support groups for disabled people. I feel like every week I am ferrying him to an event downtown." He is intellectually disabled but has an encyclopedic knowledge of the Harry Potter books. Several female classmates tested his knowledge after the session.

One week before exams and Pinterest Penelope, our class social chair, released the results of "class superlatives", one per student. One student complained about the distraction from studying: "She is just trying to sabotage us." I received, “Most likely to ask Low Yield Questions in Lecture”. Type-A Anita got, “Most Likely to Complain About Said Low Yield Question Asker”. Our lone Canadian (we have no other foreign students) got "Most likely to curse in front of a patient." Our class president received, "Most likely to use 'I'm a Doctor' line at the bar". The shy Asian received, "Most likely to ruin his/her white coat and need to order another". Dorothy Disinterested apparently does have at least some interests. She received "Most likely to hook-up with a patient" (as the social chair is also female, this did not generate any complaints to the deans).

Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: 1 day. Example fun: a "finisher prize" for the last day of class, beer and burgers with four classmates.

Year 1, Week 36

Exam week and most of us are feeling burned out. "I just want to get this over with," lamented one classmate. "Studying another few hours won't change anything."

We had four exams, three hours each, one per day, from Monday through Thursday, starting at 8:00 am or 9:00 am. All were computer-based.

The main NBME exam was challenging and surprisingly clinically-focused. Example: "Where is the lesion for someone who has right-sided intention tremor?" (Answer: right cerebellum; not everything in the brain is cross-wired.) Type-A Anita complained, "I thought it would be much more detailed and less big picture. I studied all the wrong things." There were numerous questions on peripheral nerve deficits as a result of disk herniation. Students complained that this subject was not covered in "significant detail" during lectures.

The anatomy exam, developed locally by Doctor J, was a blend of challenging second-order questions and basic identification questions, with both multiple-choice and short-answer styles. Students complained that the second-order questions as not testing only "anatomy material". For example, three students complained about questions asking to locate the lesion site for various visual field deficients. Several memorable questions started with a group of stroke symptoms and asked the student to identify the blood vessel most likely affected. Students were outraged at these applied questions. "I cannot believe Doctor J put that question in. He put that in just to screw us over."

Students were also frustrated by the locally-developed clinical exam covering the HEENT (head, ear, eye, nose, and throat) exam, the neurological exam, and child development. We looked at computer images of different retinas. Given a description of a patient's reflexes, we had to name the peripheral nerve or spinal nerve roots that might be damaged. We looked at a computer screen image of an ear canal that we would have seen through an otoscope. We were asked to identify the age of kids based on certain observable skills and behaviors. Type-A Anita complained to several classmates, "I don't need to know this for Step 1" (the board exam we will take at the end of our second year). The classmates echoed back, "I don't need to know this because I don't want to be a pediatrician." Students complained about the image quality of the ear canal, even though a higher quality image would not have helped them answer the question. Students complained, "This material overlapped with our other exams."

The patient case exam asked to propose hypotheses for various clinical scenarios. What tests would you order? What diseases should be on your differential for this given test result? What other information would you want to know? How would you manage this patient with Parkinson's? What other symptoms and test results would you expect from this patient? Most students do not study for this exam. Students complained about the drugs that were covered.

After our last exam, Jane and I went to a brewery. Students trickled in as people finished. "Cheers to another step to becoming a doctor!" Dorothy Disinterested responded, "I have lost so much faith in our medical system. It scares me to think that we are one-quarter of the way to doing stuff to patients."

Statistics for the week… Study: 15 hours. Sleep: 5 hours/night; Fun: 1 night. Example fun: We met at a classmate's apartment for pool and darts around 8:00 pm before heading downtown for an "End of M1" celebration. My classmate and I went to a less crowded part of the bar to get another beer. We were listening to a bartender's conversation with some of her friends. A friend asked the bartender, “What have you been up to since you graduated college?” She responded, “Working here pretty much.” My friend commented afterwards, "That's too bad she went to college with all that debt. She could have been the manager by now if she started after high school."

Year 1 Wrap-Up

Nearly every answer in medical school spurred another question until finally the answer wasn't known or wasn't answerable in the limited time for each subject. I eventually got used to the frustration that the system at-hand was too complex for a simple generalization. The every-two-month exam cycle gives students a sprint mentality, but I came to realize that it was okay to not know everything. Medical school is a marathon, not a sprint.

One year done and I'm more excited about working in healthcare, but disillusioned about the trajectory of American health. Diabetes, drug abuse, premature heart disease, psychosis. These are not typically driven by genetics, but rather symptoms of the society that we've built. Americans expect the healthcare system to clean up the mess, but seldom are doctors able to provide a complete cure for these ills of modern society.

I have also become disillusioned about our ability to formulate health care policy. We learned about ongoing clinical trials that pay diabetics to exercise and eat better, similar to the classic "A behavioral approach to achieving initial cocaine abstinence" (Higgins, et al. Am J Psychiatry, 1991), in which patients were given $1,000 to stay clean for 12 weeks rather than being put into rehab ($1,000 per day?). This could be much cheaper than Medicaid and Medicare paying to treat the inevitable complications. Politicians make beautiful speeches taking credit for providing insurance to millions of Americans, but where are these people who have purportedly been helped? Some of the hardest working people I met in the clinic made too much to qualify for Medicaid, but not enough to afford an Obamacare policy. They eventually have to stop work and show up in clinic with a far worse prognosis, e.g., half a foot that needs to be amputated, and the bill is paid by Medicaid or absorbed by the hospital's charity care fund.

At least in our university-run, mostly Medicaid/Medicare-funded, health care system, I didn't see obvious examples of what Jack Wennberg, the founder of clinical evaluative sciences, called "supplier-induced demand." However, my attendings would nearly always refer patients to specialists out of fear of "missing something," and every stubbed toe got an X-ray. Perhaps Wennberg's estimate that 30 percent of healthcare expenditures are unnecessary or harmful is correct, but it wasn't obvious which 30 percent we should have cut.

As a child I associated healthcare with doctors and nurses. One trip to the most popular restaurant across from the hospital campus and Jane and I realized that it was really more about administrators, lawyers, IT, and Human Resources staffers. I'm no longer surprised to see a hospital employee badge reading "business development officer" pinned to a business suit.

Classmates often wonder "Why does medical school cost so much?" Our conclusion is that the enemy may be us. Administrators and deans have proliferated along with LCME requirements in the name of creating an fair and equitable learning environment. Is it helpful to have lectures recorded? Yes, but it requires a huge IT department and expensive software. Our gym was just upgraded, which seems to have been a marketing decision because most classmates didn't know that we had an in-school gym within the school in addition to the membership at a comprehensive fitness center (with pool!) that is covered by our tuition. The Wellness Committee and the Office of Inclusion and Diversity, led by a Ph.D. psychologist, seem to have unlimited funding to hold seminars on self-defense and microaggressions (I try never to miss one due to the great catering from local restaurants); funding for student-organized events on medical topics, such as a suture workshop, is limited to $2.50 per attendee and can be challenging to obtain. Waste is noted, but seldom criticized, due to the free-flowing Federal spigot of student loan funds.

I conducted an informal survey of classmates towards the end of the year. Some of their responses are below.

What has surprised you?

"The amount of independence. You hear about all these learning environment resources, different subjects, supplemental materials for purchase like Anki and Firecracker. It is pretty overwhelming at first. I eventually realized that if I just study the exact the same way [as in undergraduate courses] then I do well. It is just school." [Jane]

"That I could actually be interested in surgery." [Disinterested Dorothy, originally planning to follow her father into internal medicine]

"People like talking about their health problems." [He obviously hadn't met my grandfather!]

Is it more or less studying than you expected? 

"Less overall but exam week is brutal. It's the way it is, not the way it should be.  I regret not being as organized and dedicated as some students. I would study more spread out instead of cramming before." [Jane]

What did you wish you knew about healthcare that you know now? 

"I always thought doctors were unquestionable. Doctors are human. Ask them questions. If they are not explaining the reason, they are not doing their job right. I now know there are good doctors and bad doctors." [let's hope that she doesn't practice these sorting skills at home; she's the daughter of a physician]

"Healthcare is challenging but it is more accessible than people would think. I approach healthcare as a field in which if you work hard enough or study long enough you can succeed. Compare this to, for example, computer programming or engineering. No matter how hard I worked at that, I just could not do it." [she majored in biology as an undergrad]

What do you like about the class and what do you not like about the class?  

"I like how our class is fun and likes to hang out with each other. We have a good sense of humor. What do I not like? Our class will complain about anything. They can also be quite disrespectful." [Jane]

Do you wish you took time off before medical school.  Gap year or no? 

"No stigma either way.  Straight in or five years out doesn't matter. Once you are here, you are here." [Youngest classmate]

"It took me three application cycles to get into a school." [Straight-Shooter Sally]

"I am glad I took a gap year. I don't think I was intellectually mature enough to go straight through. I think I would have fooled around with all the free time in medical school if I didn't learn some discipline working in the real world." [Male classmate who worked for pharmaceutical company]

"I am glad I am here, but certain specialities are off the table for me. I'm too old!" [Upperclassman who started medical school at 35]

What do you think about our teachers?  

"Passion is infectious.  When someone is passionate you can't help but listen to them. M.D.s are more fun than Ph.D.s. Teachers talk about what they know. They know their patients. That's why we are here." [undergraduate physicist major known as the class gunner]

"About a third of the instructors are great. I give an instructor one chance. If I don't like them, I no longer show up for lecture." [Classmate notoriously late for the few lectures he does attend. If the class gives him the heads up it was worthwhile, he might watch the recorded lecture online.]

What do you think about anatomy?

"I liked MSK (musculocutaneous) dissections. It was satisfying using your hands to isolate muscle and fascia layers. Reproductive was pretty cool too. I literally cut a penis in half and took the fascia layers apart. Not many people can say that! Oh, and that bone saw was sick!" [Disinterested Dorothy]

"I hate anatomy. You cannot see anything in a cadaver. So excited to be done with it." [Pinterest Penelope apparently has better things to do]

"Anatomy is the best part of medical school. It is the unique topic for medical school. All the other material a lot of us have have been to exposed to in various undergraduate majors. No one gets exposed to anatomy, at least at this level."

Anatomy Advice for M1?

"Get in there to get over. Thinking about it is bigger issue. I never had issue. Doesn't feel real because the cadavers are cold."

"It is pretty rare to have surgeons take time out of their day to spend two hours helping you dissect. Take advantage of it.  You get out what you put in. Be interested in what you are doing. It looks bad when half the class leaves early from lab." [Jane]

"Buy a pair of scrubs. You look badass and that way you won't get your normal clothes smelling like the lab." [Class Orthopod]

What are you excited about?

"Being a doctor allows you to make a decent living wherever you want to live. You don't have to live in a big city where all the jobs are for young people." [Classmate from Kansas]

"All my friends and family ask me about their health problems. It is fun to play doctor. We can now understand what is wrong with them. Ask us what to do about it? We are no better than the internet. Patient care comes from experience, not from education. I'm excited to eventually be able to answer their questions with action."

What is something you would change? 

"Administration treats us as kids, not adults. There is a resource for everything." [Classmate who juggles a newborn and toddler with medical school studies]

"The cost of tuition. The founding of for-profit medical schools tells you all you need to know." [Classmate with PA-student wife]

"Just tell me what is going to be on Step I. I do not have time nor the brain space for anything else." [Type-A Anita…]

"Residency match. If you want to do a speciality, it has become so competitive. The Match is in a death spiral." [Class Orthopod]

Following the curriculum isn't enough if you want to be a good doctor. Friends at other schools, a few classmates, and a physician mentor agree that the focus of medical school is ensuring that the lowest denominator passes, not challenging each student to reach his or her highest potential. The resources are there for anyone who wants to take the initiative, but peer pressure works in the opposite direction. The most vocal students echo each other's complaints that the curriculum isn't sufficiently test-focused.

First year for most students serves a reminder that not all of us are special. Most medical students were near the top of their undergraduate class, but that was partly because their fear of failure (failure = less than an A) was so great they didn't take challenging courses. Classmates' first reaction to getting a question wrong may be to assert that the question was unfair, poorly worded, or that the answer was not worth cramming into our already crammed brains. We expect to be the discoverer of a new drug or the manager of a big project. One of my bosses during my gap year said, "What we really need are great employees. Leadership comes afterwards." The more that I shed the entitlement mentality, the more I was able to focus on my strengths.

One thing that I learned is that medical students don't relax until a few months prior to graduation. Classmates traded their fear of not getting into their first-choice medical school for three years of anxiety of not doing well enough on Step I (end of second year) and in rotations (third year) to get into their first-choice residency. One of our clerkship directors sent us an article about the surgery residency match process: "This leaves the 163 orthopedic residencies that participate in the Match in the unenviable position of having to sort through 88,169 applications for 717 total positions from just over 1,000 total applicants." (Scott E. Porter, JAAOS, 2017)  I.e., a typical applicant applied to 88 programs, more than half of the total programs nationwide. Maybe the Web-based Match software will need to be updated with a Select All option…

More: read the rest of Medical School 2020