From our anonymous insider…
A brilliant energetic attending, straight-out of fellowship and with bright red hair to go along with both her specialty and patient (see below), led the introduction to hematology. Blood plasma is almost all water with an amalgam of solutes such as protein, glucose, amino acids, hormones, cytokines and clotting factors. The cellular components suspended in this plasma include red blood cells (erythrocytes), white blood cells (lymphocytes), and platelets (thrombocytes). All of these cellular components are made in mesh-like inner bone structures, bone marrow, home to hematopoietic stem cells which can become any of the cell constituents of blood in response to growth and differentiation signals. For example, if oxygen content is low or an individual has been bleeding, the kidney secretes the hormone erythropoietin (EPO) into the bloodstream to increase differentiation towards the erythrocyte (red) lineage.
Red blood cells are an engineering marvel and a story of sacrifice for a single purpose: transporting oxygen and carbon dioxide through the vascular network. Hematopoietic stem cells undergo a stunning transformation. The cell rearranges its membrane so the mature erythrocyte can survive intense deformations squeezing through capillary beds. The cell simultaneously begins to synthesize gobs of hemoglobin, which eventually will take up the entire intracellular volume of the cell. Hemoglobin is a marvelous contraption comprised of four oxygen-binding heme rings surrounded by four globin protein chains. Each of the four heme rings contains a reduced iron molecule at its center where oxygen binds. The globin chains are encoded in DNA and translated into an amino acid (protein) sequence. The protein scaffold modulates the oxygen-binding affinity to unload oxygen in metabolically active tissues. Genetic defects in globin genes can lead to hematological disorders such as sickle cell anemia. Lastly, red blood cells expel their nucleus and other internal organelles, such as mitochondria. Once completed, the 7-9 micrometer biconcave cell has sacrificed its ability to replicate in exchange for a slow but inevitable death. The average circulating red blood cell lasts no more than 120 days.
Our patient case dealt with a form of hereditary spherocytosis that first manifested in a person who had seemed to be a perfectly healthy 18-year-old. “Jessica” was an A-student, high school homecoming queen, and cross-country athlete. Early in her first college semester, a flu put in her bed for several days. After an apparent recovering, she became even more ill, sleeping all day and unable to leave her dorm. She had piercing pain in her left abdomen, her eyes began to turn yellow, and then her whole body. She was stabilized by a hospital Emergency Department and the next day saw her pediatrician back home — like most young adults had yet to find an internist. Her pediatrician referred her to our hematologist.
The mother interjected, “This was the scariest moment for me. [her pediatrician] would not tell us what it was, although he clearly had some idea. I called the referral office, and got put on hold. I still remember the lady’s recorded voice while on hold: ‘You have reached the Hematology-Oncology office of ….’ I was speechless! Oncology! My 18-year-old has cancer!” Our hematologist instructor continued, “Hematologists treat both cancer patients and benign blood disorders. Cancer patients almost always have hematology issues from the cancer itself, or from the chemotherapy destroying their bone marrow. I wish we could have two offices.”
Jessica recounted the first appointment. “The waiting room was scary. Almost everyone was old. It smelled of chemo and death. When the doctor spoke to us, everything settled down. She said, ‘You most likely have some sort of anemia, not cancer.'” Blood tests showed severe anemia. The left-sided abdominal swelling and pain was caused by splenomegaly, or enlargement of the spleen. The spleen filters the blood where resident macrophages eat old or damaged red blood cells. The macrophages recycle heme rings by releasing iron and bilirubin into the bloodstream. The yellow discoloration of her eyes and skin were from an excess of toxic bilirubin in her blood, or jaundice, a common affliction for newborn babies.
A basic peripheral blood smear showed that Jessica had premature, sometimes even nucleated, red blood cells in circulation. If the signal for erythropoiesis (formation of new red blood cells) such as EPO levels is high enough, the bone marrow will release premature cells such as reticulocytes. Her symptoms immediately improved after supplements of iron and folate, required during red blood cell differentiation for synthesis of functioning hemoglobin. However, doctors and the family were still at a loss regarding the cause of this flare-up after 18 years of perfect health.
Genetic testing showed a defect in a membrane receptor that causes her macrophages to eat up healthy red blood cells prematurely. Her bone marrow, without any iron and folate, could not keep up with the destruction of red blood cells. The hematologist theorized that the flu virus triggered the immune system to increase erythrocyte destruction. Jessica is now a normal college student. She continues to take iron, folate and recombinant EPO supplements. She gets tired easily, especially around exam time. Her school has given her a single room to allow her to get more sleep. She sometimes has mild left-sided abdominal pain. Her two brothers and sister attended. They had both opted out of genetic testing. Jessica said she has two fears: “having my spleen removed and needing transfusions to live. I’ve spoken to a lot of anemic patients in the waiting room who all have had to do this. I fortunately have a less severe form of spherocytosis.” The class laughed as she struggled to pronounce “spherocytosis”! She ended by saying how it is important for doctors to be cheerful and energetic. She jumped out of her seat, long red hair waving, and hugged our young hematologist. “We are best friends, redheads stick together!”
I shadowed my physician for the afternoon seeing six patients: two cases of Chronic Obstructive Pulmonary Disease (COPD, typically from smoking), a pneumonia case, a two-week follow-up after a car accident, a knee injury, and a fainting teenager. The pneumonia patient was a female in her late 60s with severe dementia and under the care of the state. A caretaker brought her in with a complaint of wheezing. She could no longer speak, but could make grunting sounds. While she tried to grab the physician’s genitals, we listened to her lungs and noted pulmonary edema in her right upper lung. We prescribed antibiotics.
The physician and I read the car accident patient’s chart. He said, “I do not know how this patient is alive.” Crashing his Ford Fusion into a stopped car at 50 miles per hour did not result in a single broken bone. He had a neck brace and terrible lacerations over his face, chest and arm, a rare success story for airbag technology given that this 65-year-old gentleman had not been wearing a seatbelt. The chart showed a history of drug and alcohol abuse, but no evidence that either was involved in the accident.
The next patient was a mid-60s grandfather who hurt his knee while playing basketball with his grandson. “Little Johnny has gotten really good. I was defending with one leg planted, and twisted. I heard a snap. I cannot put any weight on it.” I performed a knee exam and noted anterior displacement of the tibia (lower leg) with the femur (upper leg) under stress. X-rays showed no bones broken. Diagnosis: torn ACL, which unfortunately cannot heal once separated. We referred him to orthopedics for an MRI and refrained from making any Vito Corleone references.
A mature and articulate 13-year old teenager presented with recurrent episodes of fainting and dizziness. She has had these episodes for over a year, but got much worse last week and had to be taken home from school twice. I walked in first and conducted an interview and brief cardiopulmonary physical. I did not note any abnormal heart sounds upon auscultation. The mother explained her theory that the fainting was caused by beginning menstruation. During the family history, we learned that four of the mother’s eleven uncles/aunts had a heart defect requiring open-heart surgery. The doctor joined me. He did not hear any abnormal heart sounds but was clearly concerned by the family history. He ordered several tests and sent the child home with a visibly upset mother. I’m impatient for a diagnosis but will have to follow up via email.
“Geriatricians are a dying breed,” said our lecturer the next day. “No young doctors want to treat old people.” Our class supports his theory; nobody has expressed a desire to become a geriatrician. The most challenging part of interviewing the elderly for him is breaking through their fear of losing independence. Many elderly individuals will not admit if they are struggling to perform certain instrumental activities, such as driving, cooking, taking medications and even walking. Our mid-40s geriatrician stressed, “This information is the most important. Frequently, I am able to prolong their independence but I cannot help them if they do not tell me.” For example, simply using a walker could prevent an all-too-common fall resulting in a hip fracture: “A third of all patients with hip fractures die within one year.”
The class segued into a discussion. Classmates opened up with memories of the last days of their grandparents. One classmate’s grandparents committed joint suicide shortly after being admitted to a nursing home. The geriatrician offered, “I will tell you one thing: You never want to see another horrible death once you see one. I was in the army and saw a parachuter fall. That same feeling comes over me when I see patients suffer through decisions whose consequences they do not fully understand.” He concluded, “Whatever speciality you go into, you need to define what the patient wants. Physicians too often conclude clinical decisions based upon their beliefs. Some of my patients may want to live to see their grandchildren graduate school. Some just want to be able to keep walking for another year. These desires change how I care for my patient.”
Several of Jane’s college girlfriends descended into town for her birthday weekend, arriving around 9:00 pm. At dinner we somehow got on the topic of unions. Jane’s friend was passionate on the subject of the evils of right-to-work legislation and the need to force every worker to pay union dues. It turned out that she was an intern at the American Federation of Teachers (AFT). I’ll probably share her passion for unionization once I work my first 100-hour week as a resident. Jane interjected, “Shut up… today is all about me!”
Statistics for the week… Study: 15 hours. Sleep: 7 hours/night; Fun: 1 night. Example fun: Movie night with Harry Potter fans to see Fantastic Beasts and Where to Find Them; Jane dragged me along.
The Whole Book: http://tinyurl.com/MedicalSchool2020