[SOUND] Recall that the major indicator of mastitis or an inflammation in the mammary gland is this presence of these somatic cells. Again, they're coming out of the bloodstream into the milk and we're going to explore that a little bit more. But just to remind you again, that the primary ones that come in first when there's an inflammation are these polymorphonuclear neutrophils. You can see the segmented nucleus here in this particular cell and we'll get back to that in just a second, why it's segmented. After that first big wave of cells and a little bit later on in the inflammatory response, we start to get the macrophages and lymphocytes coming in. So, let's go to the next slide. So, this is a representation of an alveolus. So here's the alumen, the white part's the alumen. The yellow represents the single layer of epithelial cells with a little nuclei in there. There's a blue line around that which represents the basement membrane which is on the back side, the outside of that alveolus or the small duct and then the red little ovals here are representing capillaries. So, blood is going to be the red blood cells and white blood would be coursing through here. What happens when we have bacteria or some kind of an insult in here? There are chemotaxis factors that are basically secreted and send out that causes bacteria to come in. Let's go to the next slide and this process of the next slide, what's called diapedesis. Diapedesis, little happy faces here represent this, especially the neutrophils that leave the capillaries and then will enter in to the lumen. And then actually, what they do a lot of times they seem apparently to try to search their way around the basement membrane to find weakness work their way through that. And actually, sometimes either pop a cell out, an epithelial cell in front of them or squeeze between those cells. Again, breaking those tight junctions between the epithelial cells. Remember, we've talked before about the fact that high potassium, higher sodium, but those are diffusing. That's why you get one of the kinds of changes you'll get in the milk composition here. You get a higher sodium in milk that is from a cow that has mastitis. Go to the next slide. And so once they enter here, again, this process of going from the bloodstream through the tissue, into the milk is called diapedesis. Once they're in there, we're hoping that they're going to be digesting and phagocytizing bacteria and we'll get back that here in a second. Other things are happening, you get an increase permeability as the fluid coming out of the capillaries, so the tissue starts to swell a bit. Next slide, I just kind of indicated here. Again, you get vasodilation. So all these things are contributing to the inflammation, the swelling in the gland. And again, this can happen in the absence of an infection, in the absence of some bacterial infection. But most often, it's occurring in response to an infection. So let's take a little big closer look at phagocytosis, these little happy faces here. These polymorphonuclearnutrophylls. Just very briefly kind of think in terms of what is phagocytosis. So again, diapedesis is those cells coming out of the blood stream into the tissue. Phagocytosis occurs, there are three main components of phagocytosis. It's chemotaxis, that's a process of them finding their way to the tissue and knowing that the PMN should be coming out. Turn the diapedesis out of the capillary into the tissue, in the mammary gland versus the liver or somewhere else. So, there are chemotaxis factors. There's a whole range of things that occur there that these cells kind of a little Pac-Man shaped cells here, probably more for a nuclear neutrophils here. Ingestion, they ingest things, bacteria. So, the little red things in these case are representing the bacteria. And then hopefully, once they're internalize that they are also then digesting this bacteria and killing the bacteria. I need to kind of think about of this for just a second, because this is sound great. I mean, this what happening to most other tissues certainly in the memory gland in the other hand in addition to this glucosides coming into the milk. Non other bacteria and there's a number of bacteria, but a lot, lot more of the casing my self, the fat globules. There's a lot of other stuff for these guys to ingest and try to digest and that sometimes compromises the ability of the PMNs to do their job in the milk, in the mammary tissue. So one of the things we're seeing already is that those PMNs coming into the milk, because they are in addition to adjusting and trying to digest the bacteria, they're also trying to ingest and digest milk fat gladius in casing my cells. So again, they're already compromised, but there are other reasons why they may be compromised as well. So, let's go to the next slide. The whole range of factors that affect the ability of the memory gland and the immune system with memory gland to resist mastitis. A lot of times, the PMNs that are floating around in the blood and they're given a time had been out there for a while. The lifespan of a PMNs is not very long, so those first wave neutrophils are coming into the tissue tend to be a little bit older. And so they might not be quite as effective as some of the newer, like kind of second wave of neutrophils that might be generated. Compromised phagocytic activity of PMNs. I've talked about this in terms of ingesting or digesting or trying to digest the milk fat of the casing of my cells. Milk has low oxygen, you don't what it. They have already have very high oxygen, because you don't want to to oxidize all that milk fat and everything. So milk by its nature has very low oxygen and they're oxygen dependent mechanisms for digesting and killing, especially killing bacterial cells. And so that compromise them, because there's no a lot of oxygen around. Low glucose, phagocytic activity requires a lot of energy. It's a very, very high energy, requires a lot of ATP. Not a lot of glucose in milk to begin with. All that glucose is tied up in lactose and it's just not available in terms of providing glucose for those phagocytes, and then blockage of AC receptors. And again, this get back to some of that, all that other stuff that's kind of floating in milk, casing and so on and so forth. And potentially, block the receptors. There's these antibodies, essentially are essentially linking the mammary or the leukocyte cell to the bacteria. The bacteria, of course, being recognized by the antibody. And so if those FC receptors on the leukocyte cell are blocked, then it doesn't matter how much antibody you have on that bacterial cell. It's not necessarily going to be recognized by the PMN. And therefore, not actually ingested. In addition to all that, in addition to all those other kinds of things, there are certain bacteria. And particularly, staphylococcus aureus, staph aureus. Even if they're internalized, ingested into the leukocyte cell, they can actually resist intracellular killing during phagocytosis. So, they can actually stick around. That's part of why, one of the reasons why staph aureus we tend to associate that a lot of times with what's called chronic mastitis. Mastitis that never truly goes away. We'll talk a lot more about that in one of the future videos. So even though there's a lot of neutrophils coming in, a lot of leukocytes coming in, in terms of inflammation. It's still a bit compromised. And so, this is one of many reasons why mastitis is a particular problem in any lactating animal. So, let's take a look at what happens to tissue kind of after the inflammation and when the bacteria killed start to clear up. This is a normal mammary gland and one of the things that we might start to see is that we might to start to see, go to the next slide, some scar tissue being formed. So it could be larger than this, it could be smaller than this. Again, assuming that this gland had mastitis. So that scar tissue, because it's not going to regenerate mammary tissue, that is functional secretory mammary tissue is going to last from one lactation to another. If it's really, really bad, in other words, if there's so much scar tissue in here that this gland simply doesn't produce milk anymore. Next slide, so then we can get what's called the blind quarter. So this quarter on this cow is, this rear quarter's lactating. This quarter clearly is not lactating and probably because it had a very, very bad case of mastitis. Destroyed much of the secretory tissue in here and then even though she goes into another lactation, it doesn't regenerate that secretory tissue necessarily. So in this particular cow, we would just milk those three quarters. We wouldn't even bother to milk this particular quarter, because there's nothing being made there. What's interesting is that a lot of times, there's a compensatory response in the other three quarters. So that instead of only producing say, 75% amount of the milk, she would have produce when all four quarters were functioning. She might produce say, 85, 90% of the milk, because the other glands are actually compensating for the loss of this one gland. So, it's not a complete one to one loss there. So this video, we've started to look a little bit that host idea that is, in this case, the cow. The cow, the teat, the anatomy of the teat and those kinds of things and how they start to, things we need to kind of think about as we think about this particular disease. So, let's do a quick review of what we've talked about in this video. Streak canal, that opening in the teat is the first line of defense. It's real easy to solve the mastitis problem, which just never let that bacteria get pass that streak canal. Well, in real life well, that's a very, very, very challenging thing to do. That's why teat health and teat hygiene are so critical. That's why we spend so much time preparing the cow's utter, making sure that the teat is good and clean using genocide, teat dip and all those kinds of things on the teat. Once a bacteria gets in there or something causes an inflammation and inflammatory response, again, this idea of the leukocytes are coming out of the blood. This term called diapedesis. Leukocytes are coming out of the capillaries into the tissue and into the milk. Again, those leukocytes are the somatic cells that we've talked about before. Increased vascular permeability. So again, fluid is coming out vasodilation. These things all combine to give us some swelling of the tissue. This can be minor, it can be very severe. And phagocytosis by the PMNs member oftentimes, because they're in the milk, in the lumen of the alveoli and the ducts can be compromised, because of all the, we've talked about a number of kinds of things of why that phagocytic ability can be compromised. And then again, once the tissue has been scarred or damaged, that tissue may or may not come back into lactation. It just depends upon how extensive the damage is in the tissue. [MUSIC]
