Medical School 2020, Year 1, Week 25

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From our anonymous insider…

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.

More: http://fifthchance.com/MedicalSchool2020

Verizon Wireless in Russia

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Verizon has a $10/day “travel pass” program that lets you use your U.S. plan minutes and data in most European countries. With both my old iPhone 6 Plus and now my iPhone 7 Plus, this has proved to result in 3G service in both London and Paris, so it isn’t practical for much besides text messaging and maps.

The situation in Russia is better from a technical point of view: you get LTE data rates. It is worse from a contract point of view, however. There is a $40/month option for which you must sign up explicitly in advance. This provides only 100 minutes of voice and 100 MB of mobile data. Public WiFi is fairly common in Moscow, but sometimes you need a Russian cell phone number to activate it.

Facebook is a huge background cellular data hog, so consider deleting it from your phone altogether. I went into the “cellular” settings and shut off access to cellular data for most apps except Uber (a great service in Moscow, though the Metro and buses will get you almost anywhere), Google Maps, and Phone (iMessage uses this one? There is no separate Messages app control). I also turned off the big “Background App Refresh” switch under “General” settings. (Facebook ended up displaying some alerts, which I don’t see how it could have generated unless it was somehow still able to access cellular data.) Maybe if Apple stops concentrating on its Social Justice War it can develop a decent user interface to settings, e.g., a “minimize cellular data” wizard that asks what you really need to accomplish with the device.

The iPhone disagrees with Verizon regarding the quantity of data used. Verizon sent a text message regarding a $25 additional charge for another 100 MB data block when the phone showed only 88 MB having been used (I was careful to reset this when getting off the plane in Moscow). So I paid $65 for a week of limited usage in Moscow. My Russian friend said that he is paying $8/month for a comprehensive voice, text, and LTE data plan. So one week of roaming cost as much as eight months of domestic service. How do we get in on this business?

Medical School 2020, Year 1, Week 24

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From our anonymous insider…

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.

More: http://fifthchance.com/MedicalSchool2020

Post Office sets brain on fire

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Here’s a stamp design that I didn’t expect to see from an enterprise that gets revenue from selling stamps: “Repeal of the Stamp Act, 1766”

(Of course, if Vladimir Putin selects me as dictator to replace the Trumpenfuhrer, I will make it illegal to mail letters unless an Elvis Presley stamp is affixed.)

Medical School 2020, Year 1, Week 23

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From our anonymous insider…

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.

More: http://fifthchance.com/MedicalSchool2020

A rare moment of personal restraint on Facebook

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A friend posted the following on her Facebook feed:

At the Computer History Museum new Fellow Induction Gala. Catching up with some of the most creative people on the planet.

I want credit for refraining from posting the following comment:

It was a joint event with some other industry?

Medical School 2020, Year 1, Week 22

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From our anonymous insider…

In anatomy lab, we investigated abdominal blood vessels. The descending aorta pierces the diaphragm at the aortic hiatus to enter the abdomen where it is now called the abdominal aorta. (The external iliac artery becomes the femoral when it passes into the leg***. Being a medical student is like driving in Massachusetts where roads adopt new names every time they cross over a town border.) The abdominal aorta gives off numerous branches: the arteries of the gut (celiac, superior mesenteric and inferior mesenteric), the paired renal arteries and the gonadal arteries (testicular or ovarian). At the umbilicus (belly button) the abdominal aorta bifurcates into the right and left common iliac arteries. Each common iliac artery branches again into the internal and external iliac, which supply the pelvis and the leg, respectively. One group from last week thought they had an aortic aneurysm that was causing all the organs to be pushed forward in the abdomen. It turned out to be cancer (source unknown). They could not find any of the structures in our lab manual as the cancer mass had engulfed everything.

Our trauma surgeon, a woman in her 60s, described a frequent patient case involving the portal system (vessels that direct blood from the gut to the liver), which we dissected this week. An alcoholic presents to the ED for severe rectal bleeding or esophageal bleeding. A CT scan (Computed Tomography or 3D X-ray reconstruction) reveals liver cirrhosis, an enlarged portal vein, and tortuous blood vessels all through his GI tract.

Most blood supply to organs drains into the inferior/superior vena cava which drain into the right atrium of the heart. In a healthy person, blood supplying the GI tract (colon, intestines, spleen, pancreas, stomach and distal esophagus) drains into the portal vein. The portal vein drains into the liver for detoxification. Blood leaves the liver through the hepatic (liver) vein, which drains into the inferior vena cava to join the normal circulation.

The patient’s liver cirrhosis (hardening of the liver) caused severe portal vein hypertension (high pressure). Blood seeking an outlet drains into the lumen of the gut tube instead of through the portal system. “Portal hypertension can cause bleeding worse than getting shot in the aorta,” said the surgeon. “This is a life-or-death situation.”

Lectures continued detailing transport processes of the renal system. We learned about several drugs to treat diabetes mellitus (not to be confused with diabetes insipidus, a hormonal disease preventing urine concentration). Diabetes is named for the accompanying diuresis (excessive urination). Diabetes mellitus (mellitus means honey-sweet) is named due to the high glucose levels present in the blood plasma and urine.The severity of diabetes can be categorized as “insulin-independent” and “insulin-dependent”. Insulin-dependent diabetics require injected insulin to keep glucose levels down.

One of the most effective drugs for diabetes mellitus is metformin, which inhibits natural production of glucose from energy stores (gluconeogenesis). Metformin, derived from the French lilac (Galega officinalis), can prevent or at least delay type 2 diabetics transitioning to insulin dependence. Since at least the 1800s, this plant has been used to treat individuals with polyuria (frequent urination). By far the most common complaint is the terrible breath from metformin. The toxicologist brought a small dummy infused with metformin breath. Sally the Future Surgeon was sitting next to the dummy and threw up after five minutes. “You try to go on a date with this breath,” exclaimed the toxicologist. “Good luck!” Metformin has terrible compliance rates.

(A few hours later we were surprised when the conference room we’d planned to use was occupied by the apparently-forgotten dummy. We vacated the premises, with the smell chasing us down the hallway.)

Farxiga (Dapagliflozin), approved in 2014, is a fascinating drug for the treatment of diabetes. Farxiga inhibits SGLT, a glucose pump protein, used to reabsorb glucose in the kidney back into the blood. Patients just pee out glucose as blood plasma spills into the urinary tract. Unfortunately, this leads to unbearable urinary tract infections; bacteria love sugar.

The toxicologist brought in various insulin pens and even bought a bottle of insulin and needles. Apparently low dose insulin can be purchased over the counter although it is quite expensive. Insulin is measured in standard insulin “units”. (One unit refers to the amount required to lower glucose a set amount.) $150 for a 10 mL bottle at 100 units/mL. This might last some patients a week, others a few days. “Some severe insulin resistant diabetics use 300 units a day.”

Our patient case: “Sherry”, a 50-year-old female who has had type 2 diabetes since her late twenties. Since childhood she has been overweight, but never obese. Her whole family had a history of type 2 diabetes.

Sherry’s poor management of her diabetes led to kidney failure.(Diabetic nephropathy, degradation of the glomerulus caused by hyperglycemia, is the number one cause of kidney failure.) She joined the ranks on the dialysis wards. Dialysis filters a patient’s blood by pumping the blood through a semipermeable membrane. On one side of the membrane is the patient’s blood; on the other is a dialysis fluid (basically saline). Solutes such as glucose and electrolytes diffuse down their concentration gradient into the dilute dialysis fluid. Each dialysis session can use up to 30-50 liters of water!

Sherry described how close she got with her dialysis group. She elected to do overnight sessions. “It’s hard to get much sleep with everyone chattering and all the noises from the machines. We had a good group.” Sherry initially went only three times a week, thus requiring a large volume of blood plasma to be removed (some people go five times per week). This caused terrible cramps and muscle weakness. Fortunately, Sherry’s federal employee insurance covered home dialysis treatment and she was able to switch to a five-times-a-week schedule in the comfort of her own home. An entire room in her house was dedicated to the fluid tanks, filled monthly by truck. Because most dialysis patients have a port (brachial artery-vein autogenous fistula) installed, at-home dialysis can be done without help from a technician, but the procedure is supposed to be done when someone else is in the house in case the patient passes out.

Sherry went through seven years of dialysis. “I was at the store when my doctor called me. ‘Can you get to the hospital in 24 hours?’. ‘Yes! Yes!’ I screamed.” Sherry matched. She had a kidney donor.

“You can only appreciate this gift once you have experienced dialysis for several years. I know several transplant recipients who quickly get their kidney and just throw it away after a year. They use their new life to drink, party and have sex. They end up back in the dialysis centers. No wonder why there is strong disapproval of kidney transplants at the dialysis centers.” Sherry had retired from the federal government due to the time commitment of dialysis, but now she works part-time.

Shadowing my physician mentor this week, our first patient turned out to be a classmate. I excused myself. I also diagnosed my first patient! A 45-year-old male presented with right leg pain worsening with exertion. I asked him to lie on the examination chair and remove his pants. I then palpated his sciatic nerve, which caused a terrible radiating pain down his leg. Diagnosis: Piriformis syndrome. The sciatic nerve exits the pelvis into the thigh through a tight hole called the greater sciatic foramen. Piriformis, a muscle used for lateral rotation of the leg, can become inflamed and enlarged. This constricts the sciatic nerve causing radiating pain. He asked, “How do you make it stop?” I replied, “Let’s ask the doctor when he comes in.” Turns out there is not a great remedy. Medicine is better at labeling problems than treating them. Anti-inflammatory medications such as Tylenol and ibuprofen may help. The key is rest. Unfortunately, “George” is a construction worker without health insurance. He makes too much to be on Medicaid, but not enough to afford Obamacare premiums. I felt terrible sending him home knowing that he couldn’t afford to rest and would soon be receiving a shocking bill from the clinic.

About 20 percent of the class, and some of the faculty, went to the local women’s march, and Type-A Anita ventured to Washington, D.C. for the main event, explaining that she was demanding “equal rights for women.”

At lunch after the march, there was what would have been a discussion among eight classmates about campus sexual violence (it fell slightly short of an actual “discussion” due to the lack of interest in hearing dissenting point of views or facts that didn’t fit preconceived opinions). All supported the school-run administrative tribunals that have been expelling accused students since the 2011 “Dear Colleague” letter from the Obama Administration. Several students argued that by matriculating at school you agree to abide by the school’s code of conduct. If the school’s tribunal or committee deems an accused guilty of violating that code, that individual can be expelled without violating due process. Two classmates compared this to accusations of sexual harassment in the workplace. “A business can fire an employee if he or she is accused.” Anita: “There are far more rape cases than false accusations. 1 in 5 female college students are sexually assaulted on campus. It would be unbearable for her to live in the same dorm and go to the same class as him.”

Statistics for the week… Study: 20 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Late night bar shenanigans on the pretext of a classmate’s girlfriend arriving in town.

More: http://fifthchance.com/MedicalSchool2020

Fundamental Attribution Error on Parade in Massachusetts

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The Boston-area commuter rail system adapts the Japanese idea of trains that run every 1-2 minutes to American standards of efficiency. I.e., the trains run every 1-2 hours. A group of locals were having coffee at our town’s sole breakfast venue when we fell into a conversation with a woman from another town who had missed her train to Boston and was thus stuck waiting for 1.5 hours.

She was 53 years old, never married, and has just moved in with a 60-year-old man. He had 18- and 19-year-old children from a marriage that ended when the wife sued him under Massachusetts family law. An MIT Class of 1960 member cautioned her not to get married to her moderate-income boyfriend. Given her good career and relatively young age, she would be a prime target for a divorce-and-alimony lawsuit from this guy in the sunset of his career. She responded that both the boyfriend and everyone other divorced person that she knew in Massachusetts and New York (where she’d previously lived) had endured years of litigation with legal fees typically exceeding the cost of sending all of the children of the marriage through college. “I don’t understand why people who aren’t happy being married can’t just walk away with what they had earned,” our never-married newcomer said, “Why do they have to try to make money off their kids or their ex? One guy in New York had been cheating on his wife for three years and lying to her. Then he tried to get a share of her pension in the divorce. It took her 20 years to recover from that.”

Her model of the world was that people were fundamentally good and loving and considered their children’s welfare more important than getting maximum cash. But she had observed that all of the divorce plaintiffs with children whom she’d known were determined to get the last possible dollar for themselves out of their respective defendants, even if the result was a lot less total cash for the children (due to the legal fees and other transaction costs). How to account for the apparent discrepancy? “It is all the fault of the lawyers,” she said. “None of these people were that greedy until they hired a lawyer.”

I think this is a great example of the Fundamental attribution error, which research psychologists have shown is more prevalent among Americans than, e.g., people in India. From Wikipedia:

In social psychology, the fundamental attribution error, also known as the correspondence bias or attribution effect, is the claim that in contrast to interpretations of their own behavior, people place undue emphasis on internal characteristics of the agent (character or intention), rather than external factors, in explaining other people’s behavior.

She found it easy to believe in the evil character of all of the lawyers who had represented all of the divorce plaintiffs she knew about. She did not consider “external factors,” such as a legislative environment setting up a winner-take-all system for divorce litigants.

Related:

  • Divorce Litigation chapter (“Both attorneys are giving accurate estimates based on what they’ve heard from their respective potential clients. These irreconcilable expectations quickly turn into feelings of entitlement. People naturally get upset when they aren’t getting something to which they feel entitled. … Part of the reason that divorce litigation is so intense is what tends to happen at parties’ first meetings with attorneys. “A lawsuit never looks better than the day you file it,” one litigator told us. By definition the attorney who is interviewing only one spouse at the inception of a lawsuit hasn’t heard any of the other side’s facts. The result is that each litigant develops an expectation regarding the divorce lawsuit that is an unlikely best-case outcome.”)

Medical School 2020, Year 1, Week 21

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From our anonymous insider…

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.

More: http://fifthchance.com/MedicalSchool2020

Don’t let your kids grow up to be engineers, Part 3

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If you wondered about the practical value of academic computer science, here’s a Google PhD Summit attendee in the Everglades (90+ degrees in the shade) wearing long black pants:

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