You guys have great questions! Here are some good ones that I got last night and today.
Q. Can natural killer cells phagocytise free and circulating antigen?(pg 6 notes 1st slde) Or does the antigen have to be inside another cell and the NK cell kills the infected cell? I am confused. The book talks about NK cells killing antigen containing cells, but nothing on free floating antigen.
A. The main job of NK cells is to recognize and kill infected and damaged cells. They also recognize and kill tumor cells. What I meant to say on the slide was that NK cells can recognize antigens that are free from and unbound to MHC receptors. They can identify antigens without this kind of processing and presentation. Most of the time, the antigen is, as you note, actually present on the surface of some cell (an epithelial cell, for example, that has been infected and is presenting a bit of the virus on its surface). In those cases, the antigen is not technically free floating. It's "free" in the sense that it's not presented by an MHC receptor; but then again it's not really free-floating since it's on the surface of another cell.
But NK cells also are able to identify free-floating, unbound antigen, such as bacterial antigens on the surface of bacteria. (I guess if you want to be technical about it, bacterial antigens are also cell-bound, if you call the bacterium a cell, which it is. But that's maybe overthinking things.) They recognize this "unbound" antigen and then send signals to macrophages to go do the dirty work. So the NK cell doesn't directly phagocytize the bacterium, but it indirectly causes its death.
Q. Regarding liver regeneration, is it that there are not new cells dividing but rather it is hypertrophy?
A. When the liver recovers from an injury/insult, the cells do actually divide (they don't just get bigger, as they would in hypertrophy).
Whether you really can call the recovery process "regeneration" depends on the kind of insult to the liver. If it's a one-time toxic insult, and the underlying stromal framework is intact, the remaining liver cells divide, and the damaged areas undergo true regeneration (restoring the damaged portions of liver to their original state).
If the insult is partial hepatectomy, then the liver can't technically "regenerate" (although that's what it's called!) because the stromal framework has been disrupted (it's been removed!). It undergoes "compensatory growth" or "compensatory hyperplasia," meaning that the remaining lobes of the liver enlarge in order to compensate for what was lost. The cells do not simply get bigger in this process - they undergo cell division.
Q. Does first intention imply regeneration? Or does it only apply to scar/replacement?
A. First intention wounds are deep enough that the underlying stroma has been damaged (even if it's only a paper cut), so the process would be deemed "repair." The tissue will not be totally returned to its original state. There may be some evidence of scarring if the wound has been deep enough; and even if there is no visible scar, if you looked under the microscope, the skin in that area would not be exactly the same as before (it would be missing secondary structures such as hair follicles/sweat glands in that area).
Q. Would macrophages be considered innate or adaptive or neither?
A. Macrophages participate in both innate and adaptive immunity.
Q. Regarding immunofluorscence, should we memorize the patterns of various diseases (on p. 5 of packet on tests)?
A. NO!
Q. If you are a d, and get exposed to D (in regards to Rh factor), is there a primary immune response or only a response to a second exposure?
A. If you lack the Rh factor on your blood cells (in other words, if you are a type dd), and you get exposed to Rh-positive blood (either by transfusion or by feto-maternal hemorrhage), you will then generate anti-Rh antibodies. This process will take a while, so there will usually not be any ill effects with the first transfusion (or pregnancy). But if the patient gets exposed again (another transfusion or another pregnancy), the anti-Rh antibodies will attack the Rh-positive transfused cells, and a hemolytic transfusion reaction will occur. This can be devastating for a fetus; the condition is called hemolytic disease of the newborn and you can read more about it here.
Q. When doing a blood test for transfusion, should you perform all tests (forward, reverse, and crossmatch)?
A. Yes, that is the best way to do things, and that's the way it's almost always done. Forward and reverse typing is done on both the patient and the potential donor, and a crossmatch using donor red cells and patient serum is perfomed. If it's a life-and-death situation, and there just isn't time, then you can give the patient O negative blood and cross your fingers (and hope that the donor blood was typed correctly, and that there isn't some unusual antigen on the donor red cells to which the patient has an antibody).
Q. Should we pay close attention to the Adult Preventive Care Timeline?
A. No. I would pay attention to how the tests are chosen (what makes a test good enough to include as a preventative care measure?), and I hope that you came away from his lecture with some sense, intangible though it may be, of the thought process behind the annual or periodic physical exam.
Q. I know that mixed tumors can come from different origins, but can they be both malignant and benign?
A. There are both benign mixed tumors (for example, fibroadenoma of the breast) and malignant mixed tumors (for example, adenosarcoma of the uterus). To my knowledge, there are not any mixed tumors that have a benign component and a malignant component within the same tumor.
Q. Why are intercellular bridges indicative of SSC, what is the cause?
A. Squamous cell carcinomas can show intercellular bridges, just like normal squamous cell epithelium does. Intercellular bridges are just the connections between the epithelial cells - they are desmomal junctions by electron microscopy, but they look like little lines by light microscopy. They are useful when you have a tumor that you think might be a squamous cell carcinoma, but it's not really well-differentiated. If you see things like intercellular bridges, or keratin pearls (in which the tumor cells are trying to make keratin, but it gets all bound up in these little globs), then you can be pretty sure it has a squamous cell origin.
Q. Would cells of malignant tumors show anaplastic characteristics or can both malignant and benign show anaplastic characteristics?
A. In general, anaplasia is indicative of a malignant process. Benign tumors tend to be more well-differentiated. However, there are benign tumors that can show anaplasia - which makes their diagnosis problematic (since when you look at it, it looks "malignant").
Q. How do you determine if something is CIS, especially since it isn't metastisizing yet?
A. Excellent question! It can be difficult! Carcinoma in situ is at the far end of the dysplasia spectrum - one step beyond severe dysplasia (but one step before invasive carcinoma). However, the distinction between severe dysplasia and carcinoma in situ is difficult to make morphologically. If you ask several different pathologists to give you their opinion on whether a particular gland shows severe dysplasia or carcinoma in situ, they would undoubtedly have different opinions. So in many cases, the terms severe dysplasia and carcinoma in situ are simply combined into a single diagnostic term ("severe dysplasia/carcinoma in situ"), because they mean essentially the same thing for the patient (if left alone untreated, chances are very good that the lesion will turn into invasive carcinoma).
Q. Can dysplasia also include bizarre nuclear shapes, distinct nucleoli?
A. Yes, it can. Those are characteristics that we think of more in terms of anaplasia - but severely dysplastic cells can be very "ugly" and can sometimes have bizarre nuclear contours and distinct nucleoli.
Q. There is a picture in our notes of a malignant tumor invading the kidney, but I wrote down that it can't invade elastic tissue of a vessel, why is that, if that is true?
A. Malignant tumors have a very difficult time invading through the elastica of arteries for some reason; I'm not sure exactly why that is - maybe the strength of the elastic layer is just such that it's hard for the tumor cells to get in.
Q. Are liver and lungs also a common destination in a lymphatic spread, besides hematopoeitic spread?
A. Yes - because after the tumor cells reach the thoracic duct, they empty into the subclavian vein, and from there it's just like hematogenous spread.
Q. How well should we know the occupational carcinogens table?
A. You should know what type of malignancy each carcinogen is linked with.
We'll be talking very briefly about cardiac markers today. Here is a little summary of these markers I posted on my other blog back in August - you wouldn't have seen it so I thought I'd repost it here.
There are several laboratory tests (or “markers”) that can be used to detect myocardial infarction. They vary in sensitivity and specificity (especially in the first few hours after an infarct), and you have to correlate them with the patient’s symptoms and other co-existing medical conditions (as well as EKG and angiogram findings).
Here is a list of the tests with some pertinent facts about each:
1. Creatine kinase (total)
Creatine kinase (CK) is an enzyme present in cardiac and skeletal muscle that is released into the blood when cells are injured. An elevation in total CK means you either have skeletal muscle or cardiac muscle injury (in other words, it’s not specific for MI). This is a easy, cheap, widely-available test.
2. Creatine kinase (MB fraction)
CK has three isoenzymes: MM, MB, and BB. CK-MM and CK-MB are both found in cardiac and skeletal muscle, but CK-MB is much more specific for cardiac muscle. CK-BB is found in brain, bowel, and bladder.
CK-MB is a very good test for acute myocardial injury. It’s very specific (you don’t see elevations in CK-MB in other conditions very often), and it goes up very quickly and dramatically after MI (within 2-8 hours). It returns to normal within 1-3 days, which makes it a good test to use in diagnosing re-infarction.
Sometimes the CK total and CK-MB are reported in the form of a “cardiac index”, which is the ratio of total CK to CK-MB. This is a sensitive indicator of early MI.
Just to make things more complicated, it turns out there are two isoforms of CK-MB, conveniently called 1 and 2. CK-MB isoform 2 goes up even before the regular old CK-MB does. The results are usually reported as a ratio of isoform 2 to isoform 1; a ratio of 1.5 or more is a great indicator for early MI. However, to detect these isoforms, you have to do electrophoresis (which is a time-intensive test that has to be performed by skilled people), so the results take a while to get back.
3. Troponin I and T
Troponins are components of cardiac muscle that are released into the blood when myocardial cells are injured. They are very, very specific for myocardial muscle – even more specific than CK-MB. Troponins go up within 3-12 hours after the onset of MI (though the rise is more gradual than the steep bump you see with CK-MB). They remain elevated for a long time (5-9 days for troponin I and up to a couple weeks for troponin T), which means they’re great for diagnosing MI in the recent past (even up to a couple weeks previous to the test) but not so great for diagnosing re-infarction (unless the first infarction was over a few weeks ago). Troponin I is more specific than troponin T (which can be elevated rarely in skeletal muscle injury or renal failure).
4. Myoglobin
Myoglobin is a protein present in both skeletal and cardiac muscle that is released when cells are damaged. It’s a very sensitive indicator of muscle injury, and it’s also the first marker to go up in a myocardial infarction (even before CK-MB). It’s not specific for cardiac muscle, so you wouldn’t want to do this test as your only marker for ruling in an MI (because if the myoglobin is elevated, you wouldn’t know if it was due to an MI or a skeletal muscle injury). It is a good marker, though, for ruling out an MI (if the myoglobin is not elevated, you can be quite sure your patient hasn’t had an MI).
5. Lactate dehydrogenase
Lactate dehydrogenase (LDH) is an enzyme present in many different cells. There are 5 isoenzymes (1-5), each with different specificities for different types of tissue. In the case of cardiac injury, LDH isoenzyme 1 will go up, and usually you’ll see that isoenzyme 1 is higher than isoenzyme 2 (this is called a “flipped” pattern, because under normal circumstances, isoenzyme 2 is present in greater amounts than isoenzyme 1). The LDH starts going up in 12-24 hours following an MI, and it dissipates within a week or two. This test has been supplanted by the other markers discussed above – but you might still see older texts (or board questions, heaven forbid) that discuss this test as a marker for cardiac injury.
The best overall markers are the troponins. They have the best combination of sensitivity, specificity, and ease of test performance of all the markers. CK-MB is second best, and might be the test to do if your lab doesn’t yet do troponins (although most labs do perform troponin assays now). The first marker to go up is myoglobin (although it's not a very specific marker, which means that it’s not a good test to use for ruling in MI).
