Wednesday, December 18, 2013

WILTIMS #86: Must...sleep...

Sorry for the brief post, but I need all the study/sleep time I can get tonight.

TIL: Babies don't like getting shots, or having their nose wiped, or being looked at funny, or anything depending on the moment. Also, there seems to be at least three levels of crying: I'm not sure if I'm upset, I'm really upset, and I think I'm dying so I might as well take out your eardrums on my way out.

Even medical students don't like doing spirometry tests (myself excluded).

Tuesday, December 17, 2013

WILTIMS #85: Before the plunge

More exams are upon us, but the next couple days are blessedly light on new content. Sorry for saturating you with respiration stuff (pardon the pun), but it's all we're doing right now.

TIL: When a person exhales to their fullest extent, there is always some air left over in the lungs. This volume is important for certain clinical calculations, but cannot be determined through spirometry (measuring the volume of air going in and out of the lungs). To measure this last bit of air, known as the Residual Volume (RV), we have to use one of several other techniques. One such method is helium dilution, where the patient breaths from a known volume of an air/helium mixture. When the external mixture and the air remaining in the lungs has had time to equilibriate, the RV can be found using simple algebra.

In a normal person, the pressure in the chest is always negative. Put another way, the lungs are elastic and always trying to collapse. They continually pull on the fluid between the lungs and the chest wall, creating a suction-like effect. When a patient is on a ventilator, however, the machine is forcing air into the lungs without the chest cavity expanding, as it would with normal breath. The thoracic pressure is accordingly higher than normal. This affects fluid return to the heart, often resulting in peripheral edema (swelling of the limbs) amongst other problems. These side-effects are acceptable to keep the person breathing, but must be kept in check.

Saturday, December 14, 2013

Study Aid #7


WILTIMS #84: Mito-what?

...two freshmen high schoolers in a junior year biology class did a genetic disease report on a strange and very rare set of diseases called mitochondrial disorders. They did research using resources to which few had access because one of the kids' families was affected by this disease. Whereas his friend had always wanted to be a doctor, the kid wouldn't decide to go into medicine for several years. Little did he know that one day he would be writing in third person at medical school.

Mitochondrial diseases didn't get me interested in medicine per se, but they did turn me on to biology and set me down this path. In the years since I first investigated their peculiarities, my understanding has grown alongside that of the biomedical community. It turns out mitochondrial diseases aren't as rare as we once thought, and may still be greatly underestimated due to the difficulty that comes with diagnosing them. That's why it was so exciting that our school invited a guest lecturer to give an hour and a half long talk on mitochondrial genetics and diseases. Now 200 soon to be doctors will think of mitochondrial diseases a bit sooner in their differential diagnoses.

TIL: Azidothymidine (AZT) was the first approved HIV medication and along with other drugs that work by the same mechanism, it has the side effect of causing transient mitochondrial diseases. AZT targets the DNA reverse transcriptase of the HIV, disrupting viral replication.

Though it does not affect the nuclear replication machinery, AZT has an extremely high affinity to the DNA polymerase utilized my mitochondria. Patients thus develop all the symptoms of mitochondrial dysfunction (such as myopathy and lactic acidosis) while having this life-saving drug administered. If the side effects are severe enough, the patient may be taken off the drug, resulting in rapid recovery of mitochondrial DNA expression.

Friday, December 13, 2013

WILTIMS #83: Leeches

Sorry, not much interesting to report today. We were going over more respiration (which I've written oodles about over the last week) and the math behind genetics (which is no fun to write about). Tomorrow seems promising though!

TIL: Hemochromatosis is an autosomal recessive genetic disease caused by high levels of iron in the blood. It is one of the few diseases that can actually be treated effectively with leeches.

Autosomal dominant diseases typically are only expressed by heterozygotes (individuals with only one of the two copies of the disease gene are mutated) because the homozygous diseased genotype is almost always fatal. An example of this is achondroplastic dwarfism, the most common form of dwarfism. An exception to this rule is Huntington disease, which presents with the same disease phenotype for both heterozygotes and homozygotes.

Thursday, December 12, 2013

WILTIMS #82: Don't Panic

TIL: Giving supplemental oxygen (O2) may increase the arterial oxygen saturation but it does nothing to decrease the partial pressure of carbon dioxide in the arterial blood (PaCO2). Instead you must change the respirator settings to increase the alveolar ventilation (the amount of air that comes in and out of the lungs).

If hyperventilating get the CO2 out of your body faster, why is it so bad? Your body does not monitor its blood oxygen level directly, but instead looks at the carbon dioxide level which, theoretically, should be just as effective. If the CO2 level is high, O2 should be low and vice versa. The problem is that hyperventilation causes the CO2 level to go down without affecting the O2 level. The body responds by constricting blood vessels in the brain and other tissues, thinking that O2 must be abundant, effectively suffocating itself. This is why breathing into a bag when hyperventilating can help; it traps more CO2 in the lungs - normally a bad thing - to alert your brain to the real O2 level.

Why doesn't hyperventilating increase your blood oxygen levels? O2 is transported via the hemoglobin protein in red blood vessels and, at normal respiration rates, the hemoglobin are already saturated with O2. They can't hold any more O2, even if you are breathing more in per minute.

X-linked agammaglobulinemia (yes, I occasionally pick things to share just because they have sufficiently multisyllabic names) is a genetic immune deficiency resulting from a mutation to the X chromosome that prevents B cells from maturing. B cells are responsible for producing antibodies which are the primary weapon the immune system has to fight off pathogens. The disease is expressed far more often in males due to the X-linked recessive inheritance. As women have two X chromosomes, a woman with one diseased allele will not show symptoms but will instead be a carrier of the disease. Men (who have one X and one Y chromosome) can never be carriers and will always fully express the diseased phenotype.

Wednesday, December 11, 2013

WILTIMS #81: Do palm it pull his phat is hoc go line

TIL: Beta-thalassemia is a genetic disorder that affects the beta sub-units of the hemoglobin proteins in red blood cells. Hemoglobin are responsible for transporting carbon dioxide and oxygen to and from the lungs, so patients with beta-thalassemia often have symptoms of anemia. The disease is caused by an error in transcription from the DNA to the mRNA of the gene for the beta strand of the protein. The spliceosome, which normally cuts out the useless bits of the genetic transcript and splices back together the useful parts, for one reason or another cannot correctly remove all the fluff, which results in an altered hemoglobin protein. It can take as little as one errant nucleotide out of the over 3 billion that make up the human genome to cause this disease.

Atelectasis is the collapse of part or all of a lung. This has several causes, one being a deficiency of the surfactant secreted by the type II pneumocytes (lung cells) which reduces the surface tension of the fluid coating of the lungs, preventing the alveoli from collapsing. The chief surfactant is dipalmitoylphosphatidylcholine (which, by the way, my phone initially autocorrected as "do palm it pull his phat is hoc go line").

Atelectasis can be a problem in infants following a premature birth because, though the type II cells start producing surfactant during the 25th week, they don't begin to secrete until the 30th. The treatment is to give the mother glucocorticoids to stimulate surfactant release. Maternal diabetes can be another cause of this condition because high fetal insulin levels inhibit surfactant production. You can treat this by administering a surfactant into the infant's lungs through an intubation setup. The only problem is that the surfactant has a consistency of honey, so in order to coat the whole lung surface, you must pick up the baby and rotate them around, just as if you
were coating a ceramic pot with resin.

Tuesday, December 10, 2013

WILTIMS #80: To be or not to be

 Yesterday, my school's Ethics Club screened the documentary "How to Die in Oregon" on campus. The film follows various individuals and families, in and out of the state of Oregon, as they struggle with the incredibly difficult task of planning for an imminent and often painful death. Oregon is one of the three states that has legalized doctor assisted suicide - marketed better as "death with dignity" - which allows a doctor to write a prescription for patients with terminal illnesses to peacefully end their life at a time of their own choosing. The process is not simple and requires substantial hoop-jumping to complete.

Physician assisted suicide is distinct from euthanasia because the physician does not administer the drug them-self. The patient must be able to take the drug (usually in the form of a powder dissolved in water) unaided by anyone and they are free to change their mind at any time.

I highly recommend that, regardless of your views on the issue, you watch this documentary (it's even on Netflix streaming), though I warn you to stock up on Kleenex first. It's not terribly preachy and pretty much leaves it to the audience to sort out their own feelings based on the stories presented. Nearly everyone in the audience yesterday agreed with the law, but there was at least one person that was unconvinced, predominately on religious grounds. I would love to hear your opinion on the matter (feel free to email me if comments would be too public).

TIL: Patients with emphysema adopt a tripod position when sitting and struggling to breathe. This allows them to stabilize their shoulders with their arms, freeing the muscles of the neck to aid in respiration instead.

Heliox is a gas mixture composed of 79% helium and 21% oxygen (the same as air) that can be administered to a patient to breathe instead of air. The mixture lowers the density of air, which reduces turbulent flow and is used to treat conditions of large airway narrowing.

Saturday, December 7, 2013

WILTIMS #79: Deep breath!

Today started out rather embarrassingly. I decided to attend the weekly neurosurgery conference up at the hospital. I had never been before, so I figured I'd play it safe and wear a shirt with a collar. I had to go to class right after, so I opted for my nicest pair of jeans. Turns out that dress shirts and ties are the norm. Oops! It didn't help that today was also apparently an interview day for prospective residents, meaning that half the room was wearing suits. Joy.

Anyways, after biting the bullet and finding a hiding spot in the corner, the presentation started. The five neurosurgical residents sat in the front row and alternately led the discussion of current interesting cases and were grilled by the attendings asking what they would have done in each case (and telling them why they were wrong). Both the cases and the gauntlet were terrifying and fascinating at the same time.

I think the most disconcerting part was watching the insensitive reactions of the residents to the grim prognoses of the patients. They've seen crazy cases like this every day for years and the only way to cope is apparently to laugh. I'll definitely be going back next week (with more appropriate attire), but I'll endeavor not to be desensitized too quickly.

TIL: Dead space volume (VD) is the volume of air involved in respiration that is stuck in the trachea, bronchi and other rigid non-respiratory spaces. When you inhale, the fresh air in this space never makes it to the lungs; similarly, during exhalation some used air never makes it out of the body and gets sucked back in during the next inhalation. This is normally not an issue because the total volume inhaled is far more than the VD.

However, if you hyperventilate, taking lots of super-shallow breaths, you start increasing the proportion of each breath taken up by that used air, which eventually can lead to hypoxia and unconsciousness. Snorkels, when used improperly, can result in a similar effect. The tube of the snorkel effectively doubles your VD, meaning more stale air re-enters the lungs.

Diagram showing the various lung volumes -
Vis not shown because that volume never reaches the lungs. 
Obstructive sleep apnea is a condition that is caused by the collapse of the airway due to weak muscles that can't resist the negative pressure of inspiration during sleep. Essentially, instead of sucking in air, the lungs suck the walls of the pharynx closed, causing the patient to choke. This is treated by the administration of CPAP (or BiPAP) which involves the wearing of a mask while sleeping that helps push air into the lungs, preventing the collapse of the airway.

Thursday, December 5, 2013

WILTIMS #78: Children of the Night

TIL: Half of what we digest, we produce in the form of secretions and dead cells.

Xeroderma pigmentosa is a fascinating if awful disease. Sufferers are born without the proper cellular machinery to repair UV damage. The upshot of which is that they cannot be in the sun. Ever. Even the tiniest bit of UV light causes severe sunburn and blisters, then freckles and dark growths, and finally countless skin cancers. If caught early and followed by life-altering concessions by the child's family, children can live into their 20s (the oldest can reach their 40s).

These kids live very different lives from their unaffected peers. They must be home-schooled in their windowless home or teleconferenced into a classroom. They can only go outside at night and often convert to a mostly nocturnal lifestyle. To go anywhere, such as a doctor's office, they must be cocooned in a sleeping bag and carried around. None of these precautions are really possible in developing countries and the prognosis is far worse for affected children (see image on the left).

This disease make us remember that we take for granted how marvelously skilled our bodies are at fighting off mutations. By just walking in the sun we expose each of our skin cells to hundreds of mutations every minute. Our cells work tirelessly every moment to let us navigate the unsafe environment we live in, called Earth.

WILTIMS #77: Anarchy in the classroom!

Today we had our first Medical Ethics classes and, amusingly, our first ethical dilemma was with the class itself. We were meeting in our small groups and our instructor didn't show. At first we thought that she was just running late or going off an old schedule. 10 minutes after the latest possible start time we sent out a few students to see if the other classrooms all had their instructors and we found one other that had been similarly abandoned.

Collectively, we tried to decide what to do. Who do we contact? Do college no-show rules apply? Could they trace it back to us if we left? Is it somehow more ethically wrong to ditch an ethics class than a normal class? Eventually we decided to take our own attendance and then some people left while others interrupted another room to ask what to do. Those of us who stayed joined the neighboring room for the second half of the class.

TIL: "Up the butt" may not be the most eloquent way to explain "suppository". It is recommended we use "inserted in one's bottom or rear".

A doctor can refuse to take any patient. A doctor cannot, however, refuse to see a patient with whom they have already established a doctor-patient relationship. The doctor must give the patient a reasonable amount of time (a few months) to find another doctor before the doctor can refuse care.


Telomerase carries its own RNA primer. Let me back up a bit... DNA polymerase, the enzyme that helps make new copies of DNA from old copies, requires an RNA primer to help it initiate replication. Think of it like the little metal guide at the end of a zipper* that helps the slider attach to the teeth. The problem is that the RNA primer isn't stable and will be degraded, leaving the DNA strand a little bit shorter. To make sure that the important information coded by the DNA isn't lost after multiple cycles of replication, the cell adds a whole bunch of non-coding repeat sequences. These chromosomal end caps are called telomeres. Eventually, these do run short and need to be built back up.

That's where telomerase comes in. This is an enzyme very similar to DNA polymerase that's sole job is to add telomeric repeats to the end of chromosomes. It gets around DNA polymerase's primer problem by providing it's own primer. It then extends one strand of the DNA until it is long enough that another primer can be added and DNA polymerase can take over.

*Apparently this is called an "insertion pin" by zipper aficionados

Tuesday, December 3, 2013

WILTIMS #76: [Gasp!] What. did. you. say‽

I'm aiming for a little more sleep tonight, so this will be short and sw- uh... soapy. Yesterday's post was a doozy though, so feel free to take a gander, if you haven't already.

TIL: Washing a kid's mouth out with soap is actually quite dangerous because the soap disrupts the mucosal lining of the stomach which normally stops the stomach from digesting itself. Soap can quickly cause gastric ulcers and damage the stomach.

WILTIMS #75: Open wide?

Phew! That's the way to return from a break! I attended four hours of lecture, sat on a student panel for interviewees, participated in a pap smear workshop, and listened to a neurosurgical resident for an hour and a half as he described the crazy things he does every day.

TIL: how to give a pap smear. Also, the pap smear is named after Dr. George Papanicolaou, who invented the procedure in the 1930s.

Any given cell in the body has tens of thousands of mutations to its DNA that it is trying to repair at any given moment. That seems like a lot until you remember that any given cell has six billion base pairs of DNA. Evolution likes a nice balance between an accurate transcription mechanism (so as not to cause disease/death) and a certain degree of purposeful variation (to allow populations to differentiate and diverge).

O6-methylguanine-DNA methyltransferase is an enzyme that directly repairs a specific kind or replication mutation by transferring the aberrant modification to itself and becoming deactivated.

Borborygmi are the noises made by air and fluids moving in the intestines. Relatedly, surgeons listen to the abdomen after surgery because the stress of the procedure causes a reflex whereby the intestines stop moving. When they hear borborygmi again, it shows that the body is recovering.

Proline-rich proteins are responsible for binding tannins in red wine, making one's mouth feel dry.

If someone has a problem that causes them to drool extensively, they will not only be losing fluid volume, but also be developing a potassium deficiency. This is because saliva contains a higher concentration of potassium than blood plasma.

Cystic fibrosis is caused by a defective chloride channel.

The original test for the Mumps was to have the child suck on a lemon. The acid in the juice stimulates the salivary glands to produce and release saliva, but since they are already swollen this just causes acute pain.

Monday, December 2, 2013

Vaccines

Last week at my preceptor visit, a boy came in the office for his yearly check-up. The doctor assumed the child would be receiving his flu shot until the mother broke in, "No. Not the flu vaccine! We go through this every year." The doctor tried to quickly give the spiel as to why it's good, why it's safe, etc. but the mother would have none of it. The doctor conceded this fight - she had more people to see, this kid was fairly healthy and this mom was very stubborn.

While the doc went to answer a phone call, I sat in the waiting room. The mom from earlier came into the room with her son and found another woman that she knew, who was taking her daughter to a similar appointment. Somehow the topic of vaccines came up and Mom #1 told Mom #2 that she had refused to let her son get it. Mom #2 exclaimed, "Oh! I didn't know you could do that. I've never really liked the idea." Sure enough, ten minutes later the doctor came back to the office complaining that yet another person has refused the flu shot. The patient herself had refused, but the mother hadn't insisted either.

This little bout of contagious denial is incredibly frustrating for anyone with a background in public health. It is so easy to convince someone to opt out of vaccinations and so hard to fight back. No one likes vaccines themselves. You get stabbed with a needle, your arm usually hurts, some people don't feel 100% in the following days and, with a disease like the flu, you sometimes get sick anyways. I can't prove to you that you personally avoided getting the disease, or that you avoided passing it to your family. I can't prove to you that if you did get the flu, it was less severe.

All of the benefits of vaccines are statistical. If a large percentage of the public gets a vaccine, disease rates go down, death rates go down, and the duration and severity of illness is decreased. These benefits are proven in enormous, comprehensive studies which are repeated every few years. The same studies look at side effects. Yes, there are side effects. Some, like soreness around the injection site and a mild fever are fairly common; others, like deadly allergic reactions are so rare they can barely be shown as anything more than a statistical fluke. But on average, these reactions pale in comparison to effect of the diseases being targeted.

Take the flu, the mildest disease vaccinated against. The flu kills between 3,000 and 49,000 people in the US a year[1] varying greatly depending on the active strains. The majority of these deaths are in the elderly population, but even children, who are typically robustly healthy by comparison are susceptible. Between 50 and 200 children die each year of the flu[2] in the US alone. Over 40% are totally healthy at the time of infection. Over a third die within 3 days. 84% were unvaccinated.

Furthermore, a vaccine-defender can find him or herself battling a Gish Gallop. This is a type of argument where an attacker rapidly spouts over-simplified falsehoods so quickly that a defender cannot keep up because each reply requires a nuanced explanation of a complicated issue. Here are a few common claims and (relatively) quick rebuttals:
  • The risk from the vaccine is greater than that of the disease. Here are some data from the CDC comparing the risks for common diseases/vaccines:
    • DISEASES
      • Measles
        • Pneumonia: 6 in 100
        • Encephalitis: 1 in 1,000
        • Death: 2 in 1,000
      • Rubella
        • Congenital Rubella Syndrome: 1 in 4 (if woman becomes infected early in pregnancy)
      • Diphtheria
        • Death: 1 in 20
      • Tetanus
        • Death: 2 in 10
      • Pertussis
        • Pneumonia: 1 in 8
        • Encephalitis: 1 in 20
        • Death: 1 in 1,500
    • VACCINES
      • MMR (Measles, Mumps, Rubella)
        • Encephalitis or severe allergic reaction: 1 in 1,000,000
      • DTaP (Diphtheria, Tetanus, Pertussis)
        • Continuous crying, then full recovery: 1 in 1000
        • Convulsions or shock, then full recovery: 1 in 14,000
        • Acute encephalopathy: 0-10.5 in 1,000,000
        • Death: None proven
  • Natural immunity is better than vaccinated immunity. This one's tricky. Yes, natural immunity often lasts longer, but the added risks of a wild infection far outweigh any added risk of having to get a vaccine booster on occasion (see above statistics).
  • Giving someone more than one vaccine at a time can overload the immune system. Compared to the amount of antigens that a person is exposed to daily, vaccine introduced antigen levels are very small. Also, an activated immune system is more capable of resisting additional infection, not less.
  • Something something something... Sudden Infant Death Syndrome (SIDS). This myth shows the pitfall of our human tendency to confuse causation with correlation. Children receive their DTaP vaccinations at around the same time that SIDS deaths spike. The exact same proportion of kids who have and have not received their vaccinations die of SIDS. After extensive studying, no causal correlation has been found.
  • Something something something... autism. No vaccine has ever EVER been shown to cause autism. The one guy who published the one paper was shown to have purposefully altered the data. The paper was redacted and the guy fired and disgraced.
  • Big Pharma/doctors/etc are making tons of money off all these vaccines. Nope. If the medical industrial complex wanted to make more money, they'd hold off on the vaccines and treat patients for the conditions they'd develop. Vaccines are so unprofitable, only a handful of companies even manufacture them anymore. The big money for pharmaceutical companies is in chronic conditions like heart disease and arthritis.
Back in my preceptor's office, I tell the two doctors what I had seen in the waiting room and my preceptor's partner, being so fed up with this dangerous trend asks for the girl who refused her flu shot to come in and talk to her. The doctor starts by saying that she doesn't need to get the flu shot today, but then explains how dangerous the flu can really be, citing the same studies I linked to above. It's the best we could do at the moment. Hopefully next time she comes in, she will choose the shot, even if her stubborn mother doesn't understand the risks she is taking with her child.

If anyone has any unanswered questions regarding any vaccine, leave a comment or send me an email. I will happily research an answer and respond.