Neutrophilic Leukocytosis – White Blood Cell Pathology

00:02 Our first discussion in great detail will be neutrophilic leucocytosis.

00:07 Remember, please, a normal count of neutrophilic or WBC count should be between 4,500 to 11,000.

00:14 So, now you've noticed that your patient has an increase in WBC count, but specifically here, it's a neutrophilic count.

00:21 You have an absolute neutrophilic count greater than 7,000, where the normal limit of your neutrophil should be between 2,200 and 5,600.

00:30 If you remember-If you remember that, that's up to you.

00:33 At least know normal WBC count between 4,500-11,000.

00:38 Here we have an absolute neutrophil count being above 7,000.

00:41 Normal, 2,200-5,600.

00:44 When are you going to bring in neutrophils? Acute inflammation.

00:47 We had an entire section in which we briefly breezed through acute inflammation, where we talked about how you are then going to bring about, well, remember, circulating pool, marginating pool, we talked about rolling, adhesion, transmigration, chemotaxis and fibrocytosis.

01:07 Neutrophilic leucocytosis seen in acute inflammation, especially bacteria, infection-wise.

01:11 Sterile, well, you know about myocardial infarction.

01:15 If your patient's suffering from acute myocardial infarction, one of the first cells that you're going to bring in during acute, acute type of myocardial infarction, once again, will be neutrophils.

01:25 And remember, around the-around the third day or so, the neutrophils will then undergo apoptosis being replaced by monocytes or macrophages.

01:33 The most common drug to, then, cause neutrophilic leucocytosis would be corticosteroids in which it then causes demargination.

01:42 What that means to you is that it inhibits the adhesion molecules so that you have decreased marginating pool, neutrophil – increase in circulating pool.

01:50 Keep in mind that whenever you do a CBC and you're looking for a WBC count, in this case a neutrophil count, then you'll always going to measure the circulating pool.

02:01 Cytokines stimulation, well, we have something like interleukin 17 which is then going to stimulate the bone marrow, maybe secondary to the acute inflammation.

02:11 You require more, more, more of these neutrophils that then come out of the bone marrow.

02:16 Interleukin 17 is an important one.

02:18 In addition, when there's going to be such increased activity of your bone marrow, you can only expect, well, apart from the neutrophils that are coming out, which are normally segmented, that you might have a little bit of baby cells coming out as well.

02:31 And by baby cells, I don't mean blast and I'm not talking about hyper-segmented per se, but I'm definitely talking about band cells.

02:38 There's every possibility that during acute, acute inflammation with neutrophilic leucocytosis when there is increased regrouping of neutrophils from the bone marrow, that you might actually be recruiting in addition to neutrophils, well, increased churning out of band cells into circulation.

02:54 Hope that's clear.

02:55 This is called the left shift in pathology.

02:57 It used to be, back in the day, that if you were to then talk about maturity of cells and go from left to right, left to right; left to be very, very, very, very, very primitive cells and then as you read literally your cell in pathology, you would find that the cells are moving from left to right meaning primitive or immature to mature.

03:17 When there's neutrophilic leucocytosis, you're going to have more of a left shift more of band cells that are coming into circulation.

03:24 That you would expect to see.

03:26 Corticosteroids, we talked about this earlier, that it causes demargination, inhibits the adhesion of neutrophil.

03:33 Inhibits adhesion.

03:34 Remember the steps of adhesion? What kind of factors are involved in adhesion? Good.

03:40 We're talking about adhesion molecules such as integrins, it then binds to your adhesion molecules either VCAM or ICAM.

03:48 Here we have an extreme case of neutrophilic leucocytosis.

03:52 An extreme case.

03:54 Maybe neutrophilic leucocytosis caused by acute inflammation.

03:58 Maybe it was acute myocardial infarction.

04:00 And if that's the case, then yes, you would find your neutrophilic count to be above 7,000.

04:05 And you find your WBC count to be elevated.

04:08 An extreme case of what we're looking at here.

04:10 Your patient, maybe young child, has lymphoid hyperplasia taking place.

04:15 And the young child’s holding on down in the right lower quadrant.

04:18 Number one differential and with that type of histology that I gave you, lymphoid hyperplasia, no doubt it's appendicitis.

04:25 The appendicitis now maybe diagnosed may too late and appendicitis now ruptured.

04:31 Not good.

04:34 Peritonitis.

04:35 Maybe you have a female who's pregnant.

04:37 And now, at this point, she's exposed to the outside world, especially her urethra.

04:42 Urethra is very, very, now, quite small because of the increased pressure from the pregnancy and the fact that the size of the urethra is always smaller in a female compared to a male.

04:54 All of this making it very, very easy or increase in susceptibility for urinary tract infection.

05:00 At some point in time, however, and now your pregnant woman starts getting into the realm of sepsis.

05:05 Oh boy! Bacteraemia, septicaemia and [Inaudible 00:05:08] septic shock.

05:10 It’s two extreme cases of really, really bad conditions.

05:14 When you have such diagnosis of perforated appendicitis or sepsis, you're going to be recruiting so many neutrophils.

05:26 You have a WBC count at being above 50,000.

05:30 Think about what your normal WBC count is.

05:32 It's 4,500 to 11,000.

05:34 So, now, we have it at being 50,000.

05:36 But, why do we call this leukemoid reaction? Because it looks like leukaemia, but it's absolutely not.

05:43 "Oid", the suffix, means “appears as".

05:47 It appears as leukaemia.

05:50 Your discussion with leukaemia, you’ll understand that you are going to find increased count, but that-those cells that you're going to find in leukaemia, they're not functioning, excuse me, they're not functioning properly.

06:04 Whereas if it's leukemoid reaction, sepsis and a perforated appendicitis, the neutrophils that you're recruiting, they're all functioning.

06:13 My point is this – what is a laboratory test that you know of that assists the functionality of your neutrophil? That's called leukocyte alkaline phosphatase.

06:23 LAP, LAP, LAP.

06:26 You might have memorised this before, but sometimes you get this confused perhaps.

06:29 From now on, you won't.

06:30 And leukemoid reaction, which is not a leukaemia, but a severe, extreme case of an infection perhaps, you're going to have all this recruitment of neutrophils and they're functioning and therefore, your LAP will be sky high in leukemoid reaction.

06:48 Whereas if it's chronic myelogenous leukaemia, could you find an increase in count? Sure, you can.

06:53 But, those are cancer cells.

06:56 Cancer cells aren't working properly.

06:58 Chronic myelogenous leukaemia, you find your LAP to be decreased.

07:01 We'll talk about that one more time when we get into CML.

07:07 The second extreme case will be the following.

07:10 Now, let's say that your patient has a molecular pathology and molecular mechanism of jack two-step pathway, jack two-step pathway.

07:18 Upon reticular stain or trichrome stain of the bone marrow, you end up finding all this fibrosis.

07:24 Think about the bone marrow, please.

07:25 It should be nice and empty.

07:28 Not empty, but should be more open, huh? Cancellous bone, should be spongy, should have fat globules.

07:33 Normally, a little bit.

07:35 And then, of course, you have your stem cells.

07:37 But, instead of finding a little bit of fat vacuoles and such within the bone marrow, now you find tons of fibrosis in the bone marrow.

07:45 Or maybe, perhaps, your patient has a breast cancer, unfortunately.

07:49 And with breast cancer, let's say invasive lobular breast cancer.

07:53 And breast cancer loves to spread.

07:55 Metastasis, any metastasises to the bone marrow.

07:58 Hmm.

07:59 So, now, you have a space-occupying lesion within the bone marrow.

08:01 You have fibrosis within the bone marrow occupying it.

08:04 The normal stem cells that should be in it now are being displaced.

08:08 Those baby cells that you find in the bone marrow...

08:11 You know about megakaryocytes, you know about your nucleated RBCs, you know about your blast.

08:17 Now, these cells in the bone marrow are then being displaced, pushed out of the bone marrow, have you, by space-occupying lesion, let it be metastasis from a cancer.

08:27 I give you breast, breast cancer.

08:30 Number two, maybe it's myelofibrosis, which is a peripheral myeloid disorder.

08:36 So, when such issues take place, you're going to displace-displace the blastic cells into circulation.

08:43 Welcome to our picture of leuko(WBC)erythro(RBC)blast(baby) reaction.

08:48 So, we have all these baby WBCs, baby RBCs in circulation.

08:59 How can you confirm this? If you take a look at the peripheral blood smear, you find RBCs that are nucleated.

09:06 Pause there for a second.

09:08 Understand significance of what I just said.

09:10 Hmm, an RBC that's nucleated in peripheral blood smear? That's a baby.

09:16 You should never have an RBC nucleated in your peripheral blood smear.

09:21 But if you do, highly differential, what then is causing the space- reaction? Yet another extreme case of neutrophilic leucocytosis.

09:35 Increase in immature WBCs including myeloblasts.

09:38 Where are you finding these? In your peripheral blood smear.

09:42 Caused by infiltrated bone marrow disease or multiple fractures.

09:46 Can you see the common denominator between the last two statements? The bone marrow is being infiltrated by whom? Oh, fibrosis or breast cancer by metastasis.

09:56 Or what if the patient had multiple, multiple, multiple fractures? Obviously now, the bone marrow is going to release immature cells into circulation – welcome to our second extreme case of neutrophilic leucocytosis, known as a leukoerythroblastic picture or reaction.

10:14 Now, the extreme case is here, leukemoid reaction.

10:19 What I'm trying to show you is the following: a leukemoid reaction – we talked how, well, looks like leukaemia, but it's not.

10:26 There is no anaemia, thrombocytopenia, but there is going to be an increased number of-of blast and by that, we mean the following: looks like leukaemia.

10:36 Meaning to say that your patient here is not going to be suffering from dead bone marrow.

10:42 Right? Because of leukemoid.

10:44 What's the only thing that you're bringing out from the bone marrow? Good.

10:48 Neutrophils.

10:50 But, the patient is not going to have the leukemic symptoms of anaemia, thrombocytopenia or perhaps increased number of blast.

10:59 The only type of cells that you might find would be maybe bands and such in leukemoid reaction.

11:05 In leukoerythroblastic picture, if you’re going to take a look at the picture here, we have tear drops cells.

11:12 We have NRBC, which stands for nucleated RBCs.

11:17 And what-And what this basically means is that the...

11:19 Well, before we move on, this is a peripheral blood smear picture and what ends up happening is that if there is a bone marrow infiltration, maybe due to myelofibrosis or metastasis to the bone maybe, perhaps, from a breast cancer.

11:34 Now, you have a space-occupying lesion within the bone marrow.

11:38 The RBCs will be squeezed out and then, as it does, it hurts and it's making me cry.

11:42 It's a tear drop cell.

11:44 Alright? Literally, squeezing out of the bone marrow.

11:47 Picture that.

11:49 It's tear drop cell.

11:50 And nucleated RBC, that's a baby.

11:52 Take a look at the-the blast that you see up in the top there and it's a metamyelocyte.

11:58 All these are blasts.

11:59 This is leukoerythroblastic picture.