OUTSIDE ASSIGNMENT #1

Mechanisms of Disease – ACBS/MIC/IMB/PCOL 423/523

Spring 2018

Now that you possess just enough general pathology knowledge to be “armed” (and dangerous), here’s
the first installment of your outside assignments mentioned in your course syllabus. Some information
needed has yet to be covered, but will in the next couple of classes. And, here’s the rest of the story on
how it works. You will be given a total of 4 news media or other lay articles between now and the last
section of the course. Each article will specifically relate to topics covered in one or more of the major
sections of the course:
• Injury and Adaptation at the Cellular Level
• Inflammation and Repair
• Disorders of Circulation
• Disorders of Cell Growth
The first news article is posted at the course website: “Hummingbird deaths to close exhibit for now.”
The first article relates to the course section on Injury and Adaptation at the Cellular Level. For this and
each subsequent article, the assignment is in essence to provide a written “reverse translation” or
“rewriting” of the article's relevant lay person general language into an expanded
technical/scientific/medical/pathologic explanation of what the article is reporting or inferring, using
specific medically/scientifically correct language, terminology, and explanatory concepts learned in this
course.

HOW will you accomplish the goal of “reverse translating” or “rewriting” the lay language using
more specific and correct medical language as described above? By providing
technical/scientific/medical/general pathology-based answers to a series of questions I will provide
on each article’s lay content. Your answers will thus “expand upon” the lay language by using
your medical/pathological knowledge – this is what is meant by “reverse translation.” Another
analogy to understand the assignment would be as follows: As you read the generic lay articles, you
think to yourself… “geez that’s sure a gross oversimplification of the subject, really watered down
so that the average Joe and Jane Q. Public can understand it… as an astute individual becoming
medically/pathologically educated in the subject matter, I know what the article is really describing
or suggesting, well above and beyond the lay description.” You would then follow through with the
preceding thought by providing expanded medical/pathological answers or explanations to the questions
provided with each article.

Your collective answers to the questions for article/assignment #1 should be approximately two single
spaced pages of text (1” margins, 12 pt font). This is above and beyond the space occupied by the
questions. Please type in your answers after each question, i.e. add appropriate space for your responses
and type in your responses using the Microsoft Word version from the course website. Microsoft Word
is preferred as I have been unable to open several other word processing program docs in past years. DO
NOT DELETE, REORDER, OR IN ANY WAY CHANGE THE QUESTIONS as you add your
answers! And make sure correct formatting is preserved before you click submit.

For assignment #1, ~2 pages of answer text is considered the minimum to do the topics justice. However,
feel free to use more than two pages for your answers if you want to take full advantage of the opportunity
to review key concepts from the course, expand upon what you are learning, and seek feedback on the
particulars of your understanding or what you believe to be correct.
The primary goals of the outside assignments are as follows:

1. To help solidify the fact that what you are learning in the course actually has application to the
world as we know it (today at least). The news etc in any medium will never read the same again!

2. To be able to apply the language and principles of general pathology by taking simple lay
explanations of disease processes (which now sometimes humor you due to their simplicity) and
elaborating on these via scientific, accurate, and complete technical/medical/pathologic
explanations.

3. To provide an excellent review of selected key concepts from the course, and verify that your
understanding of same is correct (also useful for exams – that would be a hint).

4. Finally, to be able to use your newly acquired skills and knowledge base in the medical/pathology
arena to wow, OR annoy, your friends and family, depending on their nature and as you deem
most appropriate, by explaining simple health-related news to them in educated medical language.
This can be done over dinner for added impact on especially graphic topics such as necrosis and
hemorrhage etc .

If you are unclear in any way on these instructions, or the purpose and value in doing the outside
assignments, please see me for clarification until it makes sense. If you are clear on the purpose and
value of the assignment it should be educational and hopefully fun!

DUE DATE AND POINT VALUE:

The DUE DATE for your answers on outside assignment #1 is Saturday February 17, 2018, NLT 7
PM. Also note we will not have finished the material to answer all of the questions until next week. This
is an opportunity to hone your self-discipline, honker down, and turn the assignment in by the due date.
Lose the procrastinoma gene if you can! PLEASE USE THE ASSIGNMENT BOX TO SUBMIT
YOUR ASST on the D2L Course Website.

The POINT VALUE is as specified in your syllabus, i.e. the outside assignments will count for a total
of 5 points (5% for 523) to 7 points (7% for 423) of 100 possible points in calculating your final
course grade.

Questions for news article #1 follow on the next page. Enjoy!

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ACBS/MIC/IMB/PCOL 423-523 Outside Assignment Questions for News Item #1
“Hummingbird deaths to close exhibit for now”
Questions to answer using appropriate technical/scientific/medical/general pathology-based language
(i.e. “reverse-translate”) for news item #1:

1. The news article indicates that death of the Desert Museum hummingbirds was due to “iron
overload disease” from an improperly formulated (toxic iron level) lot of commercial nectar feed
solution. What is the proper medical term for systemic accumulation of iron stores to such
pathologic levels in an otherwise normal host (one word)?
The proper medical term for systemic accumulation of iron is hemosiderosis.

2. While not actually using the term “necrosis” or “oncosis”, the article infers that liver necrosis and
failure resulted from iron overload. Drawing on your knowledge of the role of transitional metals
(like Fe++) in free radical formation, briefly state how the excessive iron could have contributed to
liver necrosis. In your answer, define what a free radical is.
A free radical is a chemical species that has a single, unpaired electrons. Transition metals (such
as Fe++) can lead to the formation of free radicals. Free radicals can lead to the formation of unstable
toxic peroxides by attacking the double bonds present in polyunsaturated membrane lipids. Free
radicals can also damage DNA, mitochondria, and proteins. The combination of theses effects could
lead to necrosis of the liver.

3. Related to question #2,

a. What are the names of the major free radical species we covered that can cause tissue damage
when the balance shifts towards increased formation and/or decreased scavenging?
The three major free radical species are hydroxyl radicals, superoxide radicals, and nitric oxide
derivatives.

b. What are the major cellular targets/structures and mechanisms for free radical mediated injury?
The major targets for free radical mediated injury are membrane lipids, DNA, mitochondria, and
proteins. Free radical attack double bonds in polyunsaturated membrane lipids to form unstable toxic
peroxides. In DNA and in proteins, the free radicals attack double bonds to alter the structure of the
macromolecules. Mitochondria are damaged as a result of the free radicals attacking the double bonds in
mitochondrial DNA and the double bonds in mitochondrial proteins.

c. What are the names of the endogenous scavenging/control systems for each radical?
Superoxide dismutase controls superoxide free radicals and glutathione peroxidase controls
hydroxyl radicals.

d. What 3 major vitamins comprise the antioxidants?

Vitamin E, Vitamin C, and beta carotene

e. What is the importance of the trace mineral selenium (Se) with respect to free radical scavenging,
i.e. what function does selenium have?
Superoxide dismutase and glutathione peroxidase both require selenium in order to effectively
catalyze the decay of superoxide and hydroxyl free radicals.
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4. Other than dietary iron overload/toxicity as the hummingbirds experienced, what is at least one
additional process which can lead to localized or generalized accumulation of iron in tissues? The
answer is NOT the answer you provide for question 7.
One other way iron can build up is through blood transfusions. In cases of severe chronic
anemia, individuals may need blood transfusions regularly. This can lead to the buildup of iron in
the tissues.

5. The reporter inadvertently omitted from his/her notes the fact that the dead hummingbirds had
“generalized yellowish discoloration” of mucous (not mucus) membranes, subcutis and adipose
tissues.

a. You would refer to this “generalized (diffuse) yellowish discoloration” as ____________

(i.e. the one word medical diagnosis for same)?

Icterus

b. Considering the reported diffuse liver (hepatocellular) necrosis, briefly explain the pathogenesis
of “generalized yellowish discoloration” in such cases of liver damage.
In the case of hepatocellular disease, the liver cannot effectively process bilirubin for elimination.
Therefore, the bilirubin will build up in the liver and eventually in the blood causing yellow coloration
in the tissues.

6. What would you have expected the histopathology report on tissues from the dead hummingbirds to
have described morphologically as being iron, i.e.

a. What is the histologic appearance of iron in H/E stained sections?

Iron carries a positive charge, so it is eosinophilic. Therefore, the iron will cause the tissues to be
stained pink or red.
b. What major anatomic storage sites does it typically accumulate in (i.e. organs at gross level)?
It typically accumulates in the spleen, bone marrow, and the liver.
c. Does it accumulate intracellularly or extracellularly?
It accumulates intracellularly.
d. How would the appearance and location of iron differ from acid hematin, i.e. how would you
differentiate between the two histologically in H/E stained sections?
Acid hematin is stained brown rather than the pink or red of the eosinophilic iron. Also, acid
hematin is extracellular rather than intracellular.
e. What significance does acid hematin have, if any?
Acid hematin is essentially a contamination, so it has the potential to ruin a histologic slide.
Therefore, a sample may not be able to be used to effectively formulate a diagnosis.
f. How can acid hematin formation be easily prevented when collecting tissues for histopathology?
Acid hematin formation can be prevented by using buffered formalin and by using the proper
amount of formalin (10 mL of formalin per 1 cm3 of tissue).
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7. On a related note,
a. What is the proper medical name of the disease resulting from a genetic defect (point mutation) in
humans (also some birds, but not hummingbirds) that leads to generalized pathologic iron
accumulation and potential multi-organ failure if left untreated (one word)?
The proper medical name for this disease is hemochromatosis.

b. What is the common “lay” term for this same disease?

The common term for this disease is rusty organ disease.

c. Why does iron accumulate to potentially toxic levels in such patients (i.e. what is the primary
mechanism operative in most forms of the disease)?
Patients with the point mutation that causes hemochromatosis absorb excess iron in the intestines.
This is because the mutation causes the intestines to think that the blood is always low in iron. This
causes an increase in transferrin (the carrier protein for iron) in the blood. This ultimately leads to an
increased level of iron absorption.

8. The news article concludes by stating that “we don’t know of a treatment that’s reasonable for a bird
that weighs less than 3 grams”. Coincidentally, a close acquaintance of yours has just returned from
a visit to his/her primary care physician, indicating that he/she has been diagnosed with a disease
resulting from his/her body’s abnormal accumulation of iron (i.e. the disease you named in question
#7). Before his/her primary care physician could adequately explain the treatment options and
prognosis, the buzzer buzzed, indicating that the pre-allocated patient evaluation time decided on by
the HMO’s Board and CEO (an MBA type with little or no medical training, but a mystery pedigree
somehow warranting an 8 figure salary to “manage” your health care system and hold costs down)
had been exceeded. You can give some reassurance to your friend that they are not alone, that the
genetic defect occurs in 1 out of every ~200 people, with disease manifested in ~ 20%. Being a good
friend with medical savvy, what is a simple treatment option you can also mention to your friend to
preclude anxiety-induced ulceration of his/her gastric mucosa while he/she awaits scheduling of their
next HMO appointment?

One simple treatment is bloodletting. This effectively reduces the amount of iron in the blood. This
does not stop the absorption of iron, so the phlebotomies must be performed whenever the blood iron
levels are too high (500 mg per liter of blood). Other treatments include avoiding foods high in iron
(red meat) and increasing the consumption of foods that inhibit iron absorption (calcium, tannins,
etc.)

9. This is a question which has no single correct answer and no point value for this assignment (i.e. will
not be graded). Rather, it is an opportunity to consider and state your own brief opinion on this tragic
event and also influence that of others. The news article indicates that the hummingbird exhibit
(anticipated closure of 3 months) helps attract ~500,000 visitors per year to the Desert Museum in
Tucson. Assume admission @ ~$18/adult, and hummingbird replacement costs @ ~$15/bird, how
in general would you proceed in calculating and recouping a fair and reasonable $ figure for losses
caused by the commercial vendor that supplied the improperly formulated toxic lot of nectar?
Assume that your guiding objective is to be a decent and rational human and reach a reasonable out-
of-court settlement that is both just and which precludes economic decimation to anyone, without
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formal involvement of courts and/or tax dollars etc. And finally, appreciate the harm you could
potentially and inadvertently cause by being sloppy with your math and off just a decimal point or
so in formulating a ration or calculating a drug dosage!

If the exhibit attracts 500,000 people a year, we can assume that it attracts around 125,000 people
every three months. The total cost of admission for 125,000 people is $2.25 million. The exhibit lost
12 hummingbirds and could potentially lose 5 more. Assuming 17 birds die, the cost for 17
replacements would be $255. However, this amount is fairly insignificant when compared to the
value of admission. Therefore, I would request a settlement of $2.25 million dollars to offset the loss
of patron for the three-month period when the exhibit was closed.