Inflammation 2 PDF

INFLAMMATION 2 ​ Okay. Now. ​ 2:39 ​ Is it on? Yes. It's a good morning, and thank you for coming back. ​ 2:...

INFLAMMATION 2 ​ Okay. Now. ​ 2:39 ​ Is it on? Yes. It's a good morning, and thank you for coming back. ​ 2:52 ​ I think we'll make a start. So how many of you could actually go through the principles of inflammation? ​ 2:58 ​ So we are all aware about the definition terminologies. ​ 3:08 ​ Types of inflammation components. ​ 3:13 ​ Process and steps of inflammation and outcome. All right. ​ 3:17 ​ We are happy with this. And we are very good with the cardinal signs of inflammation symptoms that better ​ 3:21 ​ physiologic mechanism and obviously two types of inflammation for your level. ​ 3:26 ​ So moving on. Uh, we'll talk about some morphological patterns of inflammation, which can happen with acute or chronic. ​ 3:33 ​ Both. So if it says acute inflammation on your slides, just remove the acute bit. ​ 3:40 ​ Bless you. So serious inflammation. I've tried to colour code the cedars with the type of discharge we get. ​ 3:48 ​ It's a pink reddish pink discharge. So as so you can now understand this is basically transmitted which is the first thing to happen. ​ 3:54 ​ And that's because of the first second step of the uh process which is vascular dilatation permeability and angiogenesis. ​ 4:03 ​ So initially we can get pink pink watery tissue fluid which is more fluid less proteins. ​ 4:13 ​ And this is a very classical example of blisters. Many of you would have had those blisters which could be herpes simplex virus. ​ 4:19 ​ Or it could be impetigo the stuff alcohol blisters we get around the mouth. ​ 4:27 ​ So that's a very typical example. If it has got a serious discharge Burns patient I think your next patient is a burns patient next week. ​ 4:32 ​ So they begin to have transferred it. And then eventually if it gets infected that's when a transfer it usually gets converted into exudate. ​ 4:39 ​ Other than other reasons which we discussed on the other slide. ​ 4:48 ​ So very common examples are burns viral or staphylococcal blisters heart failure congestion and effusions in peritoneal. ​ 4:52 ​ The third space peritoneal space between the two zero layers this site is which is abdominal and pericardial. ​ 5:01 ​ So burns patient usually will get blisters. Normally we don't are advised to break these blisters because it is maintaining the integrity of the skin. ​ 5:08 ​ As soon as you break them, you are exposing your body to site of entry, which is organisms. ​ 5:17 ​ So hopefully do not try to break them. Uh, usually they break on their own, so that's fine. ​ 5:23 ​ But if you break them you will see that yellowish pink discharge coming out. ​ 5:30 ​ So very classical example of serous inflammation. Now we move to a bit more coming out of cells. ​ 5:34 ​ Is everybody okay? Somebody I can hear speaking. Do you want to come and lecture here for me? ​ 5:43 ​ I will be happy to sit there. Hello, friend. ​ 5:50 ​ Can I have your attention, please? Yeah. ​ 5:54 ​ It's it's, uh, it's disturbing when somebody is talking. ​ 5:58 ​ But if you want to share something, you're more than happy to come here and share with all of us. ​ 6:01 ​ So zero. Portland is as I said, now you start getting more cells, that tissue, that microbes. ​ 6:06 ​ So that's becomes an exudate or purulent or pass. ​ 6:14 ​ These are all three interchangeable terms. Pus is usually told by patient and purulent. ​ 6:17 ​ And exudate is usually speaker in used in clinical terms. ​ 6:22 ​ A very classical example I showed you yesterday was appendix. ​ 6:27 ​ So normal appendix is like your little finger even thinner than that little finger. ​ 6:30 ​ But the one we saw yesterday was quite big. And you can see here. ​ 6:35 ​ So I try my best to compare and give you normal. So you can see what features of inflammation you can see. ​ 6:38 ​ See here Cardinal signs. In the abnormal run when you compare. ​ 6:44 ​ Redness. Swelling? What else? You can see some discharge coming out from there. ​ 6:53 ​ That's the pus actually coming out from there, which is not a sign, but obviously it is telling you that possibly this is inflammation. ​ 7:01 ​ So there is swelling. There is redness. And hopefully because it was painful. ​ 7:08 ​ That's why it was removed. It's a vestigial organ. ​ 7:13 ​ It doesn't have much function, so you don't lose lost. You don't have that fifth cardinal sign very prominent here. ​ 7:17 ​ And that's a very characteristic of acute inflammation, as I said. ​ 7:23 ​ The first four features are more cardinal. So I just added a bit of yellow colour because it's zero. ​ 7:27 ​ And then you come to purulent which is yellow is discharge. ​ 7:34 ​ Now discharge could be yellow or green. Purulent discharge could be is just pus means too many leukocytes and that stuff. ​ 7:38 ​ But the colour can be because of the bugs which are causing that infection. ​ 7:45 ​ So usually with staphylococcal you get yellow. With Pseudomonas you get green right? ​ 7:49 ​ So depending on the bug, that's what it is. But what you look at is the. ​ 7:55 ​ Number of cells. And what is it made up of? So whenever we get a swab or a sample, we do a gram stain. ​ 7:59 ​ We look under the microscope and we count the white cells. How many epithelial cells are there? ​ 8:06 ​ And what if there is any gram positive, gram negative bacteria? ​ 8:10 ​ And that's how I will be able to tell you whether this is a serious or a purulent discharge. ​ 8:14 ​ So this is a very severe form. As you can understand. ​ 8:19 ​ It's usually caused by pus forming organisms, uh, which causes killing of this central part of the tissue. ​ 8:22 ​ And that's called necrosis when the cells die. You can't look at you can't actually draw the outline of the cell or the nucleus. ​ 8:29 ​ They have crumbled. And that's called necrosis. ​ 8:37 ​ Usually necrosis will stimulate inflammation. Inflammation usually will be there. ​ 8:40 ​ What is the battle physiology or physiological counterpart of necrosis which actually happens in our body. ​ 8:44 ​ Apoptosis is very good. So it is a physiological mechanism. ​ 8:52 ​ It is a programmed cell that which your body has to have it. ​ 8:56 ​ Why do we need apoptosis. What does what is its function? ​ 8:59 ​ Yep. It maintains the shape of the organ. ​ 9:16 ​ If you do not have a process, can you imagine how big your liver can be? ​ 9:20 ​ How big your intestines will be multiplying? ​ 9:24 ​ Your liver will be multiplying. So apoptosis maintains the shape and the structure of the organ. ​ 9:27 ​ And obviously as you said it, it has got, uh, embryonic value. ​ 9:33 ​ And the difference between apoptosis and necrosis is under the microscope. ​ 9:38 ​ Excellent. You do not see any associated inflammation in a process. ​ 9:52 ​ So the cell will be intact. The cell membrane does not rupture. ​ 9:56 ​ It just becomes small thicknesses. And that is why you do not get release of. ​ 10:00 ​ Lysozyme is cytokines and hence there is no chemo kinases. ​ 10:07 ​ Julia is here today. Where is Julia? She was asking me the question, uh, about, uh, uh, you know, what are the different kinases factors? ​ 10:11 ​ Julia, do you mind putting a leg down, please? For me? ​ 10:19 ​ So chemokines are not released and hence those inflammatory cells are not recognised or, uh, aligned. ​ 10:22 ​ So that's a major difference. And that's how under the microscope I will differentiate between necrosis and apoptosis. ​ 10:30 ​ Apoptotic cells will be pink small. ​ 10:37 ​ I can still see the structure but they will be pink pink and eosinophilic whereas necrosis will be very dirty lot of inflammatory cells. ​ 10:40 ​ I can hardly see the outline of the cell and the nuclear membrane. ​ 10:48 ​ Okay. So those three differences. And one is physiological, one is pathological. ​ 10:53 ​ So biogenic means plus forming organisms with all that stuff. ​ 10:58 ​ And usually they are walled by fibrous wall. So they are controlled. ​ 11:01 ​ They are limited by this fibrous wall which is a part of healing. ​ 11:06 ​ Right. The fourth stage which is resolution or healing. ​ 11:12 ​ So they do definitely have this fibrous wall which tries to contain the infection so that it doesn't spread. ​ 11:15 ​ But for any reasons, if that fibrous wall is nicked or breaks open then it has a tendency to spread. ​ 11:21 ​ And the other problem with these lesions is because they have a fibrous wall. ​ 11:27 ​ And usually these fibrous walls are a vascular. ​ 11:31 ​ So if you want to treat these patients with antibiotics. What antibiotics we will use and what route will you use? ​ 11:35 ​ They are a vascular. They have some vessels, but not as rich as other places would have. ​ 11:44 ​ Any pharmacist here. Will you use oral route, I.V. route or local route? ​ 11:52 ​ Local is good. So you put a needle. ​ 12:03 ​ Australians are not very brave to put needle. Americans are very brave and even Indians are very brave. ​ 12:07 ​ We try to put needle wherever we can so that we can spread and offload the pressure. ​ 12:12 ​ This is full of gunk. Gunk means that person necrosis. ​ 12:18 ​ Your patient is crying of pain. Instant thing is surgical knife. ​ 12:22 ​ You slit the open it and you try to offload it either by a needle or by a knife. ​ 12:27 ​ So that's the best treatment for these patients. ​ 12:32 ​ Secondly, either you give locals, you take the pass out and you give something local or else local will only be effective for certain while. ​ 12:35 ​ So you give them I.V. antibiotics, hoping that something will go through that little I.V. and genetic vessels. ​ 12:44 ​ But you definitely have no role of oral antibiotics. Oral antibiotics will not penetrate. ​ 12:50 ​ And you give antibiotics, which will have good serum concentration and is specific for the tissue. ​ 12:56 ​ Certain antibiotics get concentrated in the urine. ​ 13:03 ​ So if you have got urine abscess, renal abscess, you give antibiotics which penetrate the kidney tissue better. ​ 13:06 ​ Certain antibiotics have better penetration and belly retract and so on and so forth. ​ 13:12 ​ Right. Certain antibiotics can cross blood brain barrier. ​ 13:16 ​ So if you have got a cerebral abscess you can't just give simple antibiotics which do not cross the blood brain barrier. ​ 13:20 ​ So everybody is happy with that. And we usually try to give Seidl antibiotics, antibiotics which kill the bug, not just. ​ 13:27 ​ Halt the growth of multiplication, but they have to literally kill the bugs so that they don't multiply. ​ 13:34 ​ Know for pharmacology. So that's what we do. ​ 13:41 ​ So access excellent example is abscess in the knee. ​ 13:46 ​ Septic arthritis I believe is your patient right. ​ 13:50 ​ And then obviously, you know Boyle's particules these they can be small upsets. ​ 13:55 ​ Big ups's ups's in the liver, kidney, brain, lungs anyway. ​ 13:59 ​ But most classical example is knee joint infections. ​ 14:05 ​ You can see here right. Purulent discharge. It's like telling you. ​ 14:10 ​ That I am purulent inflammation. You do not even have to think about it. ​ 14:14 ​ But you can't nick these knees just in the words, unless you've made sure that they are not going deep down to the bone. ​ 14:20 ​ So normally we do not neck these knees here. As such, it has burst open so it's going to discharge. ​ 14:26 ​ But we take them to the theatre and under aseptic uh, precautions we operate among them. ​ 14:31 ​ Fibrin inflammation is. So now you can say transmuted. ​ 14:38 ​ Which is vasodilation, vascular permeability. Then cellular events are starting to creep in. ​ 14:44 ​ So now you get more purulent. And then eventually the fibrous component which is healing will start to creep in. ​ 14:49 ​ So certain infections have more fibrous tissue. And these are called fibrin inflammation. ​ 14:55 ​ Very classical example is pericarditis inflammation of the pericardial layers of the heart. ​ 15:00 ​ Now I have an experiment for you to go home and do it. ​ 15:08 ​ All of you have bread and butter at home. So go home. ​ 15:11 ​ Take two slices of bread. Put butter on it. Nice. ​ 15:16 ​ Not solid butter if not refrigerated like room temperature. ​ 15:20 ​ And then peel those. Separate those two bread apart. ​ 15:23 ​ And tell me what you see. You will see Sabrina's pericarditis. ​ 15:27 ​ You will see those dots of butter actually poking out. ​ 15:34 ​ That's an excellent example of Sabrina's pericarditis. ​ 15:38 ​ So people who are sitting here, they might be able to see here, you can see here. ​ 15:41 ​ That buttery thing which has come up. So that's normal heart. ​ 15:46 ​ You can see here. It's rough. That's pericarditis. ​ 15:51 ​ That is February. Nurse pericarditis this bit. I'm sorry. ​ 15:56 ​ You might not be able to appreciate it, but you are more than welcome to come and have it. ​ 16:00 ​ So this is because of the rubbing of two layers of. Uh, visceral and is a layer of the pericardium. ​ 16:05 ​ And in between is the pus. So that's two slices of bread and pus. ​ 16:12 ​ Is the butter here. Right? So that's forbidden as pericarditis, as the name suggests. ​ 16:16 ​ It has got a lot of Sabrina brain tissue. They will usually heal back to normal depending on how much of a brain tissue you have got. ​ 16:21 ​ But if they do not heal, the patient gets constrictive pericarditis because it becomes tight. ​ 16:30 ​ Fibrous tissue is not that elastic. So it becomes tight and it obviously tries to push on the heart. ​ 16:35 ​ And as a result of this the patient is not good with their volumes diastolic and systolic volumes. ​ 16:41 ​ And that's how they get heart failure. So that's a very classical example. ​ 16:47 ​ You can get the same in peritoneum as it is. ​ 16:53 ​ You can get that in pleura you got which is called as pleural rub. ​ 16:56 ​ If you put a stethoscope on these patients pericardium, if they have pericarditis or pluralities or peritonitis, ​ 17:00 ​ you will be able to hear that rub excuse as then the heart is beating, you will be able to hear that rub. ​ 17:07 ​ And that's classical of fibrin as pericarditis. So I have told you how to look at it, go home and do the blood experiment and how to auscultation it. ​ 17:14 ​ And then feeling is obviously you can feel that butter on the bread. So look listen and feel is pericarditis. ​ 17:24 ​ Here it is because of the mesothelioma cells which secrete fibrinogen that gets deposited in between the two layers. ​ 17:30 ​ So that's fibrin pericarditis. Maybe somewhat here, but it's more evident on the pericardium. ​ 17:37 ​ Not much on the heart. Everybody's happy. ​ 17:45 ​ So some people had questions yesterday and I was really happy because they were thinking beyond, ​ 17:50 ​ you know, what Sabrina would look like, what Portland would look like. So that's a great example of you guys thinking ahead. ​ 17:55 ​ So now we start with chronic inflammation. So chronic, as Tom suggests. ​ 18:03 ​ How long should the duration should of symptoms should be? Greater than six weeks, right? ​ 18:08 ​ So greater than six weeks will be the completion of the patient. ​ 18:15 ​ Whatever the complaint is, depending on the system, inflammation of prolonged duration greater than six weeks, even up to years. ​ 18:18 ​ It is characterised by mononuclear cell infiltration which is usually lymphocytes, monocytes and macrophages. ​ 18:25 ​ So lymphocytes and monocytes are blood cells. And when they get into the tissue the monocytes they become macrophages.  ​ 18:33 ​ Right. So that's what you get. There is lot of tissue destruction. ​ 18:40 ​ The original tissue whatever it is gets usually destroyed and replaced by fibrous tissue. ​ 18:44 ​ The repair is more by fibrosis and a bit of angiogenesis formation of blood vessels. ​ 18:51 ​ So in contrast to acute you see the last component more prominent here along with cellular component. ​ 18:58 ​ So in acute it's the vaso vascular and cellular. ​ 19:05 ​ Whereas here it is more fibrosis plus cellular. ​ 19:09 ​ Right. So this is a very classical example of pneumonia. ​ 19:14 ​ Somebody has got TB. These are the alveoli. ​ 19:18 ​ Can you see the difference here? Alveoli are empty here and not congested. ​ 19:21 ​ What we saw in acute inflammation pneumonia which was flooded with neutrophils and vasodilation. ​ 19:25 ​ The interstitial septa was rich in blood vessels here you can see some here and there but not much. ​ 19:33 ​ But in the interstitial septa not in actually in the alveoli. ​ 19:40 ​ Here you can see a lot of chronic inflammation in the septum. But you can also have it in the alveolar spaces. ​ 19:45 ​ But here it's showing more in the septum. And this is the pink fibrous tissue which is replacing the normal alveolar interstitial tissue and alveoli. ​ 19:52 ​ And that's why they have shortness of breath because the tissue is not there which is supposed to do the exchange of oxygen. ​ 20:01 ​ Between the alveoli and the black. So what are the causes of chronic inflammation? ​ 20:10 ​ You know, we did vindicate for acute and same thing you can do here. ​ 20:16 ​ But good news is with chronic inflammation that are not many to many causes. ​ 20:20 ​ Most of the common causes are infections. And they are specific to pathogens. ​ 20:26 ​ For example tuberculosis Mycobacterium leprosy is another mycobacterium which is leprae. ​ 20:30 ​ You do not get to see Mycobacterium leprae here. ​ 20:36 ​ There are certain areas, for example, when you go to east coast of India, there you see a lot of leprosy. ​ 20:39 ​ Right. So mycobacterium family usually causes chronic infection syphilis Trypanosoma pallidum. ​ 20:45 ​ We are seeing a big surge of syphilis recently. It is because of a lot of international travel and change in sexual practices. ​ 20:51 ​ So, uh, that's, you know, MSM and change in sexual practices. ​ 20:59 ​ That's leading to a lot of syphilis. ​ 21:03 ​ So why are they making it mandatory for syphilis screening to be done in pregnant females, especially antenatal care. ​ 21:05 ​ Certain viruses like EBV. ​ 21:12 ​ Uh, herpes viruses. They can cause, uh, chronic inflammation. ​ 21:17 ​ Fungi. Fungus can easily cause chronic inflammation. ​ 21:22 ​ And we'll talk about this in my lecture next week. ​ 21:28 ​ I think it's on Wednesday. An opportunistic infection. We will dwell a bit more on fungal infections, but mainly uh, these are mucosa fungi. ​ 21:31 ​ You know the fungi again experiment. Put your bread outside in sunlight for three four days and you will see that greenish mould coming on it. ​ 21:40 ​ That's actually fungus. That's a mucus fungus right. ​ 21:48 ​ So that fungus can cause chronic inflammation. That's how penicillin antibiotic was discovered. ​ 21:52 ​ Penicillium. Penicillium is actually a fungus. ​ 21:59 ​ And from that the penicillin antibiotic was discovered. ​ 22:03 ​ Parasites. Most of the parasites, they can either cause eosinophilic acute inflammation or they can cause chronic mononuclear inflammation. ​ 22:07 ​ Also, depending on what type of parasite they are, are they worms or are they, uh, you know, non worm type and that we will do in year two. ​ 22:17 ​ But for you guys just remember few of the causes. ​ 22:27 ​ Now the importance of this is why these pathogens I'm not saying bacteria or virus pathogens means it can be bacteria fungus parasite or virus. ​ 22:30 ​ Why they need chronic inflammation because chronic inflammation characteristically happens in those, ​ 22:40 ​ uh, pathogens where you need intracellular killing. The bugs have to be trapped within those inflammatory cells like lymphocytes or monocytes. ​ 22:47 ​ And the killing will happen within the cell. Not outside the cell. ​ 22:56 ​ Intracellular killing. And that's why these are very chronic and difficult to treat and difficult to diagnose. ​ 23:01 ​ Because I have to find that white cell which has a bacteria, and my stain has to go through that lymphocyte into the bacteria to stain it. ​ 23:07 ​ So they are not easy. And that's why the ask for three sputum smears in TB. ​ 23:15 ​ Because they are interested. Now, these things are not written in books, guys. ​ 23:22 ​ This is all coming from my 35 years of experience. Nobody will say why we do three. ​ 23:26 ​ Yes, they will say, because TB has to be open TB, ​ 23:31 ​ you have to be spitting it out in the sputum to be diagnosing it, which may not be the case in every patient. ​ 23:35 ​ Open TB means the bronchus is connected to the infected cavity. ​ 23:40 ​ Then only the cavity will drain into the bronchus. And when you cough, you cough that material which is in the bronchus and then only you detect. ​ 23:45 ​ So that is one of the most biggest criteria. But the second criteria is they are intracellular. ​ 23:52 ​ Right. And that's why we need to give antibiotics, which can penetrate these cells. ​ 23:58 ​ Which is ironic. I saw an isoniazid rifampicin virus in amide. ​ 24:04 ​ And it it all for drug therapy a so that it can get into those cells. ​ 24:09 ​ And B you do not develop resistance. So now you can understand why you get three specimens and why they are difficult to diagnose and treat. ​ 24:14 ​ It is because we need. They are intracellular bugs. ​ 24:21 ​ So PCR usually is a good technique or detection of chemokines what they release. ​ 24:25 ​ This is a indirect method how we diagnose TB and we will come to that in the lecture later. ​ 24:31 ​ So always try to think about these books. The second most common cause is so we have an eye for infection.  ​ 24:37 ​ And then the second one is for toxins. Toxins are also very common like silica silica fibres, asbestos, asbestos sheets are banned. ​ 24:45 ​ Now in construction you can't use them. So people who work in factories which are, uh, dealing with coal, silica, asbestos for longer period of time, ​ 24:55 ​ they will not present with just symptoms or lung disease, interstitial lung disease. ​ 25:05 ​ They will usually have a history of working in those industries for 2030 years. ​ 25:11 ​ Right. So interstitial lung disease from silica asbestosis usually will come with chronic inflammation atherosclerosis. ​ 25:16 ​ Has anybody thought that myocardial infarction actually is an inflammatory disease. ​ 25:24 ​ The atherosclerotic plaques, which are made up of fat, cholesterol free fatty acids, ​ 25:29 ​ platelets and obviously complement factors and little bit of fibrin. ​ 25:35 ​ That plaque is actually the stimulus for causing. ​ 25:41 ​ Am I? So that plaque is inflammatory and that causes chronic. ​ 25:46 ​ You don't usually you don't get heart failure or heart attack overnight when you have developed atherosclerosis. ​ 25:51 ​ Do you know that we are sometimes actually born with fat streaks? ​ 25:59 ​ If you look at the arteries of kids, babies, infants, neonates. ​ 26:03 ​ You might even actually find some fatty streaks. We are actually born with fatty sticks, but then it's up to us to keep them under control. ​ 26:08 ​ Depending on our modifiable and non modifiable factors. ​ 26:14 ​ So over a period of time, they start building up to the extent that they block the corner reversals. ​ 26:19 ​ And that's when your heart is crying of blood hypoxia, that infarction. ​ 26:26 ​ So atherosclerosis is a very good example. Obesity. ​ 26:33 ​ Obesity is now labelled as an inflammatory disease. It's actually a disease. ​ 26:38 ​ It is not something pathophysiological or just a norm away from physiology. ​ 26:42 ​ And the free fatty acids actually act as a stimulus in obesity to incite inflammation. ​ 26:47 ​ Suture material. Many times we have heard that patients have had surgery,  ​ 26:53 ​ and a part of the suture material didn't dissolve or if they had non absorbable sutures means sutures. ​ 26:58 ​ We don't get absorbed by the body. They have been left behind. ​ 27:03 ​ And that suture can actually form suture. Oh mom or mom is swelling along the suture because suture is a foreign body. ​ 27:07 ​ Other it can be a plastic or it can be a thread proline or uh, like krill and stuff like that. ​ 27:14 ​ Right. So that can actually stimulate an inflammatory reaction. ​ 27:21 ​ So suture is a, uh, stimulus that and it can cause, uh, suture. ​ 27:25 ​ We don't usually say suture. Right. Is we say suture. ​ 27:30 ​ Oh, mom, usually, you know, some terms are different, even though if it's inflammation. ​ 27:34 ​ Gout. If you remember, I showed you that toe yesterday. ​ 27:39 ​ Gouty toe. It is a chronic inflammation because they have got excess uric acid deposits going into the synovial membranes of the joints, ​ 27:42 ​ mainly the metacarpal and pharyngeal joints. It's a chronic disease. ​ 27:51 ​ But then they get acute attacks in between. And that is why it's called acute on chronic. ​ 27:56 ​ So there is another fourth terminology. Now I'm introducing. ​ 28:01 ​ You have got acute, you have got subacute, you got chronic. ​ 28:05 ​ And then you can have acute on chronic. Right? ​ 28:09 ​ So when you have a chronic process, you are living with it without any problem. ​ 28:12 ​ But then something precipitates the acute attacks. ​ 28:17 ​ For example, if you take if you are stressed or if you eat something or take something which increases your uric acid levels, ​ 28:19 ​ or if you are not able to excrete that uric acid, you get more deposition and it hits a level where you get that acute pain. ​ 28:27 ​ Five senses of cardinal. So that's gout. So uric acid crystals are the stimulus that. ​ 28:35 ​ So I t and a. ​ 28:41 ​ In training assessment. You guys have to do it when you come in year 4 or 5. ​ 28:45 ​ So that's the pneumonic. You can remember infection toxins. ​ 28:50 ​ And obviously immune mediated toxin could be foreign material also like suture and uric acid. ​ 28:54 ​ Immune mediated is autoimmunity is a very classical example of chronic inflammation. ​ 29:00 ​ Auto immune means auto antigens, which evoke self-perpetuating immune reaction leading to tissue damage and inflammation, which is prolonged. ​ 29:06 ​ Classical example rheumatoid arthritis. Inflammatory bowel disease. ​ 29:14 ​ As you can see here, a lot of inflammatory cells in the bowel. ​ 29:19 ​ And those are the obviously glands. So that's the mucosa mucosa. ​ 29:22 ​ Psoriasis. This is a lady with malar flush. ​ 29:26 ​ Butterfly flush. You have this case in here too as one of your uh. ​ 29:30 ​ First part of your semester two for Makaha. ​ 29:36 ​ And that's because of lupus antigens. The lupus antigens have antibodies anti lupus antibodies. ​ 29:40 ​ And that causes inflammation. Hashimoto's thyroiditis. ​ 29:47 ​ It's an inflammation of thyroid because you have antibodies against the thyroid globulins. ​ 29:51 ​ Antigens. So that's again an anti uh it's a chronic inflammatory disease. ​ 29:57 ​ Pernicious anaemia. It is a type of anaemia. ​ 30:01 ​ Micro macro Citic anaemia which you will do in year two. ​ 30:04 ​ Bigger red versus than normal. It's because of they have anti uh intrinsic factor antibodies. ​ 30:08 ​ These patients have antibodies against the intrinsic factor which is actually helpful in absorption of vitamin B12 and folate. ​ 30:16 ​ And as a result of which because they have antibodies they are not able to absorb B12 and folate. ​ 30:24 ​ And if you go back to your biochemistry, B12 and folate is very important in electro genesis, right. ​ 30:28 ​ Tetra hydro folate and all that stuff. Maturation of nucleus, cell, cytoplasm, and nucleus. ​ 30:36 ​ And mainly it's that. So either it's autoimmunity antibodies against the antigens or abnormal immune response. ​ 30:44 ​ You may not have antigens against your antibodies against your antigens, but the response is abnormal. ​ 30:51 ​ It's not what you are expecting especially with inflammatory bowel disease. ​ 30:57 ​ Right. So abnormal immune response or auto immune response. ​ 31:01 ​ So those are two different types of immune mediated diseases. ​ 31:06 ​ Everybody's happy. So that's as best I think that's asbestosis or silicosis where you get a lot of black deposition in the lungs. ​ 31:09 ​ And that's what it looks like. And that's what it looks like under the microscope. ​ 31:19 ​ And obviously it heals by fibrosis. ​ 31:25 ​ So I've shown you one example of asbestosis there and one SLA and one IBD. ​ 31:28 ​ So one is abnormal immune response and one is autoimmune response. ​ 31:34 ​ So I can just give you some case scenarios while I will try to tell you what the diagnosis said. ​ 31:39 ​ And then I might ask you what type of inflammation it is or what is the stimulus there. ​ 31:44 ​ Well, you know which cellular component is more. So you can start. ​ 31:48 ​ So now I'm training you between yourselves. Make groups and make questions. ​ 31:52 ​ Silly questions. Okay. To begin with. And then develop on that as you go through your file. ​ 31:57 ​ You can make your own questions and share their use there. ​ 32:03 ​ There is a student called Rahal. I don't know if you guys know him. He's in year five. ​ 32:07 ​ That's how he started doing it. He started making questions. Sometimes he would send me initially and I would encourage him, but then I said, ​ 32:11 ​ I don't have time, so don't keep sending me because he would send me 15 questions too. ​ 32:17 ​ Two quality assured, which is good idea, but sorry, I don't have resources. ​ 32:21 ​ So I told him share it between you guys and maybe give it to your seniors. ​ 32:26 ​ Maybe donate those questions in your question bank. And improvise on that.  ​ 32:30 ​ So that's how you can make your own assessment questions. ​ 32:35 ​ And if they are good, if you write good questions, I sometimes use your questions also because they go in the student bank and I use them, ​ 32:38 ​ I tweak them here and there, and I actually feed back to the student who has written that what I have done, and we use those questions. ​ 32:47 ​ So I'm encouraging you guys to write your own questions so that you get them in the exams. ​ 32:54 ​ Good. So let's start with the story here. ​ 33:00 ​ We have a history of a 41 year old male who presents to Gold Coast University ​ 33:03 ​ Hospital outpatients with four months history of low grade fever of 37.7. ​ 33:10 ​ Now, another thing I want you guys to train is when you read clinical stories, don't jump to diagnosis. ​ 33:16 ​ This is the time when you have to chunk it, chunk the information and try to derive some. ​ 33:24 ​ Outcome of it. What does it mean? So the first line says 41 year old male, middle aged four months history of low grade fever. ​ 33:31 ​ So there is fever. But it is low grade. ​ 33:41 ​ It is grumbling. And what is the duration? So you should start thinking. ​ 33:46 ​ What is happening here? Is this inflammation? He's got fever. ​ 33:54 ​ And the duration is four months. So possibly chronic inflammation, that's the first thing which would come to your mind. ​ 33:59 ​ Now you should think. Does he have any more features? Let me ask. ​ 34:07 ​ Let me see. So what? What are the features he has got? He has got bilateral dull, aching upper chest pain, productive cough with yellow sputum. ​ 34:10 ​ So now you can see the features of inflammation are coming here. ​ 34:18 ​ He has got pain. He's got loss of function. He has got fever and a history. ​ 34:22 ​ Productive sputum. So now we are actually going getting into chronic inflammation. ​ 34:28 ​ He recently noticed blood in his sputum. Why did he not come to us for four months and why now? ​ 34:33 ​ Blood is what brought him. You know, whenever you see blood, you panic.  ​ 34:41 ​ So he's coughing up blood in his freedom. And that's why he comes to me now. ​ 34:46 ​ And when I ask him, he says, this has been going on for four weeks, for months, but now he's sitting blood and that's how he comes to me. ​ 34:51 ​ He has lost eight kilograms of weight. Right. ​ 34:58 ​ So he's possibly not eating properly. He's malnourished. ​ 35:02 ​ Maybe because he's not eating properly, maybe because of the disease. ​ 35:05 ​ The clinician runs a battery of tests, including chest X-ray, which is here. ​ 35:09 ​ You guys are not expected to read chest X-ray, but certain things I will show you here. ​ 35:14 ​ It might be a good idea to remember those couple of them. So here you can see that's the chest. ​ 35:19 ​ That's the heart. Obviously it's like this. ​ 35:25 ​ So that's the left side of the chest. That's the right side of the chest. And you can see a cavity there. ​ 35:29 ​ That's the cavity. That's the abscess or biogenic inflammation in the lungs. ​ 35:34 ​ And you can see a lot of white shapes in the lower lobar. ​ 35:40 ​ It's infiltration right. Infiltration because of inflammation. ​ 35:43 ​ So this patient is classical TB apical TB with lots of consolidation or inflammation in the lungs bilaterally. ​ 35:48 ​ Now x haemoglobin is ten. His haemoglobin is low because he's anaemic. ​ 35:59 ​ Because it's a chronic disease. You have anaemia of chronic disease. ​ 36:04 ​ So possibly he has got chronic disease. The bugs are eating up his iron. ​ 36:08 ​ Possibly. And maybe he's malnourished. He's not eating properly and that's why he's losing weight. ​ 36:12 ​ White cell count total is 19,600. Is that normal? ​ 36:17 ​ What is that raised white cell count called in medical terminology. ​ 36:22 ​ Leukocyte is right. Leukocyte ptosis. ​ 36:27 ​ Is that? And I am telling you which type of leukocyte ptosis. ​ 36:31 ​ That's a differential count. Which different type of white cell is raised of the total white cell? ​ 36:35 ​ If you remember yesterday I said 60 to 70% of neutrophils 20 to 30% are lymphocytes. ​ 36:41 ​ Is I usually 3 to 6%. Monocytes are usually around 1 to 2%. ​ 36:46 ​ And whether you are lucky to see one in your whole life. ​ 36:52 ​ 0.0 to 0.1%. Right. So the differential is mainly lymphocytes 80% rather than 20 to 30 which is the reference range. ​ 36:57 ​ It's 80% of lymphocytes. They have even out beaten the neutrophils. ​ 37:06 ​ So now what do you think? You have got the history. ​ 37:11 ​ You have got the chest X-ray to see the glass lungs. And now you got the blood counts. ​ 37:15 ​ What are you now thinking? What type of inflammation is this? ​ 37:19 ​ Chronic. I don't want the diagnosis at the moment, guys. Right. We have not. ​ 37:27 ​ We can't come to the diagnosis yet. We can just say it's a chronic inflammation maybe of his lungs. ​ 37:30 ​ That's what I want you to progress. That's how. ​ 37:36 ​ Now I'm telling you, he's advised to submit early morning sputum on three consecutive days, which is positive for a pathogen on a special stain. ​ 37:41 ​ That's his early morning sputum. Why do we ask for early morning sputum? ​ 37:49 ​ Because when you are sleeping at night, everything gets concentrated. ​ 37:54 ​ The urine gets concentrated because you have not read for 8 hours or 6 hours, ​ 37:57 ​ and the sputum in the lungs gets concentrated because you have not coughed up. ​ 38:01 ​ So there are high chances that this concentrated sputum will have concentrated bacteria. ​ 38:05 ​ Right. So we asked for early morning sputum and at least three sputum on consecutive days. ​ 38:11 ​ Possibly. Otherwise they can have a gap. And again, I told you why we need three sputum. ​ 38:16 ​ Because hard turns to find this intracellular pathogen which may not be open TB. ​ 38:21 ​ Now you can see here. It's not gram sustainable. ​ 38:27 ​ You can't. Gram stain this bacteria. You need a special stain for that which is called zeal. ​ 38:31 ​ Nails and stains and stain. And hence, if you do not write to me, query TB. ​ 38:37 ​ I do not do that. Do not stain on every pus or every sputum. ​ 38:44 ​ They will usually get Grahamston, but they don't get certain stains. So even one iota of doubt. ​ 38:48 ​ You write it and I will do a certain stain. The reason why they don't get stained with Grahamston. ​ 38:54 ​ We will come to that. So just remember it's a special stain called zeal needles instead. ​ 39:00 ​ So those are your epithelial cells of the lungs maybe or maybe lymphocytes. ​ 39:04 ​ And these are all the pink thin beaded bacteria bacilli. ​ 39:09 ​ These are bacilli mycobacteria is Mycobacterium bacillus TB complex. ​ 39:14 ​ So that's what it is. So what is happening here. Inflammation maybe chronic inflammation. ​ 39:21 ​ What more could you ask? Did he have TB? ​ 39:27 ​ You don't just capture TB like that, especially in Western world because it's not endemic. ​ 39:31 ​ It's not hanging in the environment, but in countries like sub Indian continent or South America or South Africa or, ​ 39:36 ​ uh, Russia, Middle East, it's endemic. ​ 39:45 ​ It's there in the environment if you are immuno compromised. ​ 39:48 ​ You can inhale it and you can get TB, right. So you have to ask for history of contact in Australia. ​ 39:52 ​ Did he have contact with somebody who had TB or did he travel to any of this high risk endemic areas or is he immuno compromised? ​ 40:00 ​ Because if he was from one of these endemic countries, he would have had TB as a childhood or maybe in earlier years, but not seen. ​ 40:10 ​ Evidently it was a silent infection sitting. Because TB can be a latent infection. ​ 40:21 ​ It can sit in your lungs without harming you as a friend. ​ 40:25 ​ But when you become immunocompromised for any reason, like your on steroids or your energy malnourished, ​ 40:29 ​ or you are taking anti-cancer drugs, or you are taking monoclonal antibodies, ​ 40:35 ​ or if you are diabetic or renal failure, which is again a type of immuno compromised, ​ 40:39 ​ and or somebody becomes pregnant, which is physiologically immuno compromised. ​ 40:43 ​ And this TB bacilli which is sleeping can get activated. ​ 40:47 ​ And that's called reactivation of TB. ​ 40:51 ​ And that is what you see in the clinical world, right. ​ 40:55 ​ So you ask for history travel and immunosuppression. ​ 40:59 ​ What symptoms bring to the hospital. We have done that. What stay in significance. ​ 41:03 ​ What why. So we have covered all of that. Anybody has got any questions? ​ 41:07 ​ Thank you, Alex, for nodding your head. So what is TB Michael bacterium. ​ 41:15 ​ Tuberculosis is also called as TB complex. ​ 41:22 ​ It is a slender beaded pink bacteria which is non gram sustainable but acid fast bacilli. ​ 41:26 ​ And that is why you need a special stain. Acid fast bacilli means it. ​ 41:33 ​ Cell wall is rich in my colleague acid. It has a complex lipid which is called my colleague acid. ​ 41:38 ​ And that's why the name Michael bacterium the Michael my colleague acid is very complex. ​ 41:43 ​ And actually it is not gram tenable. It resists decolonisation by acid alcohol and retains the primary stain which is acid fast, the carbon version. ​ 41:49 ​ And that's why it's dense pink. It is a different process. ​ 42:01 ​ You have to burn the Gerber version underneath it for five minutes, ​ 42:05 ​ and then obviously decolonise it with acid alcohol and then try to do a secondary stain, ​ 42:08 ​ which is the counter stain, the saffron, and then look under the microscope. ​ 42:14 ​ TB bacilli. Determination is an art. Because it will not be that flow readily present on the slide unless your patient has got severe TB. ​ 42:19 ​ So you have to have that knack or art, and that usually comes if you have seen these type of slides very commonly. ​ 42:29 ​ So in India, if you guys get a chance to go to capstone in India in year five, you will actually go to this place where they have TB camps. ​ 42:36 ​ You will be seeing 500 TB patients in a day sitting underneath a tree. ​ 42:43 ​ Obviously you wear mask and you eat well so that you don't get STB. ​ 42:47 ​ I haven't got TB. I have been working there. ​ 42:52 ​ So it is not that if you just come in contact, you get TB. There are a lot of factors. ​ 42:55 ​ The triangle I was talking about. Host environment and the pathogen. ​ 42:58 ​ So you have to really look for 100 fields before you tell it's negative. ​ 43:04 ​ So it comes with an expertise. But nowadays we do apple fluorescence microscopy. ​ 43:09 ​ We stain it with some fluorescent stains and it will. ​ 43:13 ​ Shine is a apple green fluorescent bug, so it's easy. ​ 43:18 ​ It's an objective method, not a subjective method, because subjective means I have to look for these bacteria under the microscope. ​ 43:23 ​ But now it's converted into objective fluorescence microscopy, which usually is done at Brisbane. ​ 43:29 ​ So you send me the sputum, I send it to Brisbane. They will instantly do an apple fluorescence microscopy or a certain stain and they will tell us. ​ 43:34 ​ Right. Or you can do a PCR. It's a slow growing bacteria. ​ 43:43 ​ It takes ten weeks to grow in solid media, and that is why it's a chronic inflammation. ​ 43:48 ​ It is a chronic disease because even in body, once you acquire it, you don't get symptoms within 2 or 3 days. ​ 43:53 ​ 2 to 3 months because it takes a while to grow, right? ​ 44:00 ​ Only when it grows it can produce all those cytokines and cause problem or disease. ​ 44:05 ​ And the media, which we used to use nowadays, they are only used for antibiotic sensitivity or for, uh, typing and stuff like that. ​ 44:11 ​ This is an egg media. It has a bit of egg. So TB is likes nutrition. ​ 44:19 ​ LJ is Lowenstein Jensen Media. It has got egg so that they can grow. ​ 44:24 ​ And then when they grow we have uh indicator phenol blue. ​ 44:28 ​ It will phenol green bit will change colour to yellow. And that's the TB bacteria. ​ 44:33 ​ So every week I will bring out those bottles and I will look if it is growing. ​ 44:37 ​ And I will do this for 12 weeks. But now it is all automation. ​ 44:41 ​ We don't do this. ​ 44:46 ​ We just put a bit of sputum in this liquid micro growth indicator to midget right micro growth indicator tube, which is a liquid culture media. ​ 44:47 ​ I put little bit of sputum in there and I put it in the machine. ​ 44:58 ​ And when the bugs grow, there will be change in the wavelength or there will be change in the turbidity of the solution. ​ 45:01 ​ And that is what is picked up by the machine. ​ 45:09 ​ It will start beeping when it goes to a certain level, because the rays are not able to penetrate through it. ​ 45:11 ​ And that's when I will say it is positive. So because it is a micro growth, it happens very quickly. ​ 45:17 ​ I can detect it in less than 12 weeks in my machine. ​ 45:23 ​ So that's the beauty of growing it in micro growth indicator tube. ​ 45:28 ​ You can grow them. How do they get transmitted? They get transmitted through airborne. ​ 45:32 ​ Somebody who is positive with TB. The cavity is connected to the bronchus. ​ 45:37 ​ When they cough they shed those bacteria in the sputum in the environment. ​ 45:42 ​ And if you are standing near them, you inhale them. ​ 45:47 ​ Doesn't mean you get TB. You will have the bug. ​ 45:51 ​ But for some reasons, if the triangle is not working within you, the host immunity, the pathogen virulence, and the environment. ​ 45:54 ​ Then you get TB, right? So aerosol. ​ 46:03 ​ So that's why you will see TB patients. We ask them to wear masks and we keep them in a single room which is negative pressure room. ​ 46:07 ​ You understand what is negative pressure room. Things from inside cannot come outside. ​ 46:15 ​ Pressure is negative inside things from outside. Positive pressure will flow into negative pressure. ​ 46:21 ​ But where the patient is inside because his he is coughing. ​ 46:26 ​ TB you don't want his TB to come out. So it's negative pressure room. ​ 46:30 ​ So there is an anti room where you go and change your clothes of PPE and then you go inside. ​ 46:35 ​ Not everybody is allowed to go inside a patient's room. ​ 46:40 ​ Who has got TB. So that's what TB is. ​ 46:43 ​ Risk factors is countries where there is overcrowding poor light sanitation because some can kill it. ​ 46:48 ​ Poverty immunosuppression, malnutrition. My MD project which was my MBBS project was on TB. ​ 46:55 ​ So I went to 100 patients houses and I did 100 controls to see their bio socioeconomic status of living. ​ 47:01 ​ What was their house like, how many rooms were there? How many people were sharing the house? ​ 47:10 ​ What was the ventilation like? What was their nutrition like? ​ 47:15 ​ What was their income like? Did they had any immunosuppression? ​ 47:18 ​ That was my MBBS project. ​ 47:22 ​ It was fun and I could actually relate with so many patients, like in one room of three by three, which is like very small room. ​ 47:25 ​ Ten people would be living with no sunlight. So that's how it spreads. ​ 47:35 ​ So they might have acquired from somewhere. And then obviously they will spread within the family. ​ 47:40 ​ So it's a, uh, very, uh, very much disease of. ​ 47:45 ​ Uh, overcrowding. But having said that, TB has come back in resource rich countries like Australia, UK and America. ​ 47:52 ​ The reason is not overcrowding. The reason is immunosuppression. ​ 48:01 ​ Right we are. Advanced with treatment. ​ 48:07 ​ We are trying to treat people with immunosuppressive agents. So that's one of the reason why TB is coming back, especially with HIV 1981. ​ 48:10 ​ It came back in Western world. So the people believe that TB is a poor man's disease that doesn't exist anymore. ​ 48:19 ​ It can be a disease of rich or poor man, depending on how and where they are living and what they are. ​ 48:28 ​ Uh, if they're immunosuppressed or not. So everybody is happy with this. ​ 48:35 ​ TB experts. So how does TV happen? ​ 48:43 ​ Or how does this chronic inflammation happen? So let's take an example. ​ 48:48 ​ Henry. Henry is in Australia. He goes to India, or maybe he is in contact with somebody who has got TB. ​ 48:53 ​ Oh, let me put mine myself. I do, I do give him three TB right. ​ 49:02 ​ I was going to use my own example as a separate, because you are somebody who has never lived in an endemic area. ​ 49:08 ​ That was, let's say, man X, who is not exposed to TB by ever. ​ 49:13 ​ And now he goes to maybe either his immunocompromised in contact with a TB in Western world, or they visit a country where TB is an environment. ​ 49:19 ​ So they will inhale the TB bacilli which is there. ​ 49:30 ​ That's a TB. Basically they inhale it. Now as we know it is a chronic. ​ 49:33 ​ It is a bug which will stimulate chronic inflammation. So monocytes, lymphocytes will be stimulated. ​ 49:39 ​ Macrophages which are in our lungs. Alveolar macrophages. ​ 49:44 ​ They will entrap these bacteria. If you remember we were talking about. ​ 49:49 ​ Recognition recruitment and engulf ment phagosome. So they will entrap it and they will try to sort of control it. ​ 49:53 ​ And that's where it's intracellular in a figure. Uh macrophage or lysosome. ​ 50:00 ​ So to get TB you have to have those receptors. ​ 50:05 ​ On your macrophages, then only it will be internalised. ​ 50:11 ​ Right. And that's why everyone doesn't get TB. So you internalise in your macrophage. ​ 50:15 ​ It tries to kill by doing uh you know all those process of cytokines chemokines vagal you know hypochlorite and all that stuff back. ​ 50:19 ​ TBIs is a smart bacteria. It actually manipulates your endosome processes. ​ 50:30 ​ It doesn't allow it to be killed. It takes over the engine of lysosome activity and it survives. ​ 50:35 ​ It survives, and then it gets into the lymphatics and it spreads to the lymph nodes and also spills into the blood. ​ 50:44 ​ And you get a bacteraemia, a low grade flu like illness you will get you will be a bit headache, ​ 50:51 ​ flu like illness, body ache, malaise, little bit of cough. ​ 50:57 ​ Some lymph nodes here and there. But you will ignore this as a flu like illness. ​ 51:01 ​ And that's called primary TB. You are exposed to the TB first time. ​ 51:05 ​ You are not sensitised to it. You are exposed to it the first time you get a small primary bacteraemia. ​ 51:11 ​ But the beauty of this is it is very temporary and then it is honed in these lymph nodes or maybe macrophages, ​ 51:17 ​ and it stays there happily is actually entrapped by a fibrous capsule. ​ 51:26 ​ So it will be there in your lungs somewhere. Fibrous capsule. ​ 51:33 ​ And you don't get any symptoms and signs because it doesn't cause any damage to your lungs. ​ 51:37 ​ It's just sitting there, sleeping there. So that's primary TB. ​ 51:43 ​ Now if this same man x. For some reasons he becomes immunocompromised or he again becomes comes in contact with virulent TB or. ​ 51:48 ​ Uh, for any reasons. He becomes immuno compromised. This TB, which was sleeping in his lungs, gets reactivated, it wakes up and it gets activated. ​ 52:02 ​ And now the whole process starts. What happens is these molecular, uh, these, uh, macrophages, ​ 52:12 ​ which have that sleeping TB bacteria within the fibrous capsule, it will get activated, start releasing cytokines. ​ 52:18 ​ It will start showing that MHC class two receptor and the TB antigen. ​ 52:25 ​ Obviously it will be passed in the presence of interleukin 12 which is released by the macrophages.  ​ 52:30 ​ It will actually pass it on to the lymphocytes T lymphocytes which is a chronic inflammation right.