The Silent Killer In Our Midst And Post-Mortem (i.e. Midterm Exam) Results Are Back

I'm referencing an immune response, which isn't always pathological or part of a disease process. Yes, folks, the silent killer in our midst is... inflammation-- dum da dum! In Chapter 2 of the eighth edition of Robbins and Cotran's _Pathologic Basis Of Disease_ they state:

Inflammation may contribute to a variety of diseases that are not thought to be primarily due to abnormal host responses. For instance, chronic inflammation may play a role in atherosclerosis, type 2 diabetes, degenerative disorders like Alzheimer's disease, and cancer. In recognition of the wide-ranging harmful consequences of inflammation, the lay press has rather melodramatically referred to it as "the silent killer."

I remember reading a very interesting Scientific American article called "Heart Health In The Inflammation Age" about the role of inflammation in heart disease (and how inflammation stemming from dental disease may even be a risk factor for myocardial infarction).

More than that didn't make much sense to me until today, when we started our section on cancer. Dr. Levine explains the link between chronic inflammation and cancer in my 'Cancer Principles' handout:

Proliferating cells are more susceptible to acquiring mutations that contribute to tumor progression. Any factor that promotes chronic proliferation will increase the likelihood that an individual will develop cancer. Examples include: estrogen, which stimulates the proliferation of mammary and ovarian tissue; toxic chemicals including ethanol, which kills cells thereby promoting the proliferation of stem cells and hepatitis C virus, which promotes chronic inflammation of the liver, thereby stimulating hepatocyte proliferation. These factors act as indirect carcinogens because they don't directly mutagenize DNA. Chronic inflammation is especially dangerous because in addition to growth factors (promoters) secreted by neutrophils and macrophages, these cells also produce large amounts of reactive oxygen species which can act as initiators and mutagenize DNA.

What reactive oxygen species is he speaking of? I can flip to Dr. Clark's lecture (or Robbins and Cotran) and see that neutrophils produce superoxide, which is turned into hydrogen peroxide, which undergoes a further reaction to become hyperchlorous acid, i.e. bleach via myeloperoxidase. Macrophages form hydroxyl radicals rather than bleach (since they lack myeloperoxidase) and these react with reactive nitrogen intermediates to form the powerful peroxynitrite intermediate. (Cool aside: myeloperoxidase has a heme group which when combined with its bromine cofactor gives neutrophil rich secretions the greenish hue that you may be familiar with in substances such as pus or mucus).

What can you do about all this to prevent yourself from being struck down by the silent killer in our midst? Besides brushing your teeth and not sharing blood or bodily fluids (which will prevent you from contracting hepatitis C and a whole lot of other nasty viruses)? Robbins and Cotran illuminate:

Another approach to manipulating inflammatory responses has been to modify the intake and content of dietary lipids by increasing the consumption of fish oil. The proposed explanation for the effectiveness of this approach is that the polyunsaturated fatty acids in fish oil serve as poor substrates for conversion to active metabolites by both the cyclooxygenase and lipoxygenase pathways but are excellent substrates for the production of anti-inflammatory lipid products called resolvins and protectins.

Hence the big deal over omega-3 and -6 supplements, eating fish being good for your heart, and the many cereals and even peanut butter products that have flaxseed in them (I don't know if flaxseed is just as good as fish oil-- it is high in omega-3 but I'm not sure how bioavailable it is).

So brush your teeth, pratice safe sex, eat fish or take supplements with fish oil and you may evade the silent killer.

But lest you forget the original function of inflammation, I leave you with this pearl of wisdom from Dr. Buckle's lecture notes: As a clinican or pathologist remember, inflammation is the morphological manifestation of the immune response.

Now, back to the post-mortem. I'm thrilled with my midterm results. I'm very motivated to study hard for the final in hopes of getting a truly good grade. I guess my seasonal affective disorder can't keep me from succeeding academically. Phew.