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.
When does Jane finally divorce him?
@jack
soon, my precious, sooooon…..