Medical School 2020, Year 1, Week 19

From our anonymous insider…

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.


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