Transcription
Okay, let's talk about restrictive lung diseases. So, restrictive lung diseases may lead to a decrease in lung volumes, a decrease in the FVC and TLC. PFTs are normal, but in very high-yield guys, this thing is just a blur in the mind that you have an increase in the FEV1 to FVC ratio. You will have a normal or increased FEV1 to FVC ratio. If you see that anywhere, you're just going to think about restrictive lung diseases.
Okay, and if you see, so if you see again, if you see you have a normal or increased FEV1 to FVC ratio, it's restrictive. If you see there is anything decreased in these values, you're going to think about obstructive right away. I mean, you see it, you right away think about these two diseases.
Okay, so now let's look at the patients. Patients may present with short, shallow breathing. Types or altered respiratory mechanisms. That's one of the types. This is extrapulmonary. You have a normal DLCO in this case. You have a normal A-a gradient. You have respiratory muscle weakness, basically. In which case would you have respiratory muscle weakness? Polio, myasthenia gravis, Guillain-Barré syndrome, ALS. And the other one is chest wall abnormalities. Where would you have that? In scoliosis, severe obesity.
So again, if we just read what we talked about, we said respiratory mechanism, there's an altered respiratory mechanism. An altered respiratory mechanism which is extrapulmonary is something which is respiratory muscle weakness or chest wall weakness. That's one of the types.
The other type is diffuse parenchymal lung disease, also called interstitial lung disease. Interstitial lung disease is a pulmonary cause. There's going to be a decrease in DLCO. That's in comparison with your normal DLCO and the normal A-a gradient. But here, you just have an increase in the A-a gradient. Pneumoconiosis, diffuse parenchymal lung injury like interstitial lung diseases. What are the diseases in it? You can have interstitial lung disease with pneumoconiosis, which are your coal workers' pneumoconiosis, silicosis, asbestosis. You can have sarcoidosis, which is basically bilateral hilar lymphadenopathy, non-caseating granulomas, increase in ACE and calcium levels. Idiopathic pulmonary fibrosis, granulomatosis with polyangiitis, pulmonary Langerhans cell histiocytosis, which is eosinophilic granuloma, hypersensitivity pneumonitis, drug toxicity like for example, bleomycin, busulfan, amiodarone, methotrexate.
So all it is is a BAM BAM. So BAM is what? B-A-M. B-A-M or you can just call it BB-AM. What is BAM? Bleomycin, amiodarone, and methotrexate. And these are all drug toxicities which cause parenchymal lung disease or interstitial lung disease. And then the last one is acute respiratory distress syndrome, which also causes all of that.
Now, the other thing that is very high yield is radiation-induced lung injuries, also causing parenchymal lung disease, in which it is associated with pro-inflammatory cytokine release, in which you have TNF-alpha, IL-1, IL-6. TNF-alpha, IL-1, IL-6 may be asymptomatic, but most common symptoms are dry cough and dyspnea, low-grade fever. Acute radiation pneumonitis develops within three. Very high yield, this is important. So acute one will develop three to twelve weeks, within three to twelve weeks of radiation, which is called the exudative phase. But radiation fibrosis can develop after six to twelve months. So acute radiation pneumonitis, meaning inflammation, will occur within three to twelve weeks, which is the exudative phase. But the fibrosis will eventually occur months after the radiation. Months after the radiation.
So, I mean, this is all just memory-based, guys. And got nothing here, just memory. But what's different is if you have some restrictive lung disease, how are you going to know? You're going to know that by right here, increased or normal FEV1 to FVC ratio. And you see normal DLCO or normal A-a gradient, you think about extrapulmonary. But if the DLCO is decreased and there's an increase in A-a gradient, you think about pulmonary disease.
What are the pulmonary diseases? Pneumoconiosis, sarcoidosis, eosinophilic granulomatosis, pulmonary Langerhans cell histiocytosis, hypersensitivity, drug toxicity. Drug? What are the drugs? BAM. BAM is the drug toxicity. Acute respiratory distress syndrome, and your radiation use. Radiation. What is radiation going to do? Well, radiation is going to cause a release of the pro-inflammatory cytokines. That radiation that you give is going to release the cytokines. Which cytokines? Nothing extra here. TNF-alpha, IL-1, IL-6. TNF-alpha, IL-1, and IL-6. Yeah.
So that's how can we memorize that? So radiation, radiation, right? Radiation. A-1 and R is like six. T-alpha, TNF-alpha, alpha for A. Alpha. I mean, just remember A-1. Radiation, you know, when you want to have a radiation, you want to have, you want to go to a good place for radiation, right? You want to go to some nice CT scan place, some nice X-ray. You say, "Hey, I want, I want to look at some, some good, some good technology." So A-1 plays for radiation. So TNF-alpha is from A. TNF-alpha plus your IL-1. A-1. And your radiation is for six. I mean, this is one of the things. If you have a better one, please drop it down in the comment section. You know, I would love to see it. But okay, so we got the BAM here and we got this TNF-alpha and IL-6. It could be asymptomatic, but again, it's just going to be presented dry cough, nothing else, with a low-grade fever. Dry cough, low-grade fever. After radiation, you think about pneumonitis, which can occur within three to twelve weeks. But the fibrosis will occur within six to twelve months.
Moving on with the specific one, which is idiopathic pulmonary fibrosis. IPF. Idiopathic pulmonary fibrosis. Okay, let's look at this one. It is a progressive, progressive fibrotic lung disease of unknown etiology. Amazing, unknown etiology. You know, that's a good thing. So we don't have to memorize more. It's just unknown. But let's see. Main walls, multiple cycles. Multiple cycles of lung injury, there's inflammation, there's fibrosis. Lung injury. So many cycles of lung injury, persistent lung injury, multiple lung injuries with inflammation and fibrosis causes fibrosis. That's a simple thing, right? Idiopathic, we don't know the cause. Pulmonary is talking about lungs. Fibrotic lung has been fibrosed. No rocket science here. Associated with somebody who's tobacco smoking. Anything, just put it on tobacco. Anything, put it on tobacco smoking. Environmental pollutants, genetic defects.
What are the findings? You have progressive dyspnea, fatigue, nonproductive cough. You have crackles. I mean, you have fibrosis, why would you have a productive cough here? I mean, look, you have fibrosis, you don't have any production. Productive cough, man. Crackles, clubbing. Important. Clubbing is important. Imaging will show peripheral reticular, reticular opacities. Important. With traction bronchiectasis. Traction bronchiectasis plus minus honeycomb appearance of the lung. Within the advanced honeycomb appearance is simple. You know, you just have all these small, you know, small appearance of like in a honeycomb appearance, meaning small lung fibrosis that you see and you say it's a honeycomb appearance. After long, which is seen in only in advanced disease, by the way.
Histopathology. Histopathology. I mean, histologic pattern is usually interstitial pneumonia with decrease in type one pneumocytes. What were the type one pneumocytes? They were covering 97% of the alveoli. They were the squamous cells, right? They would line the whole alveoli. And in them, they had the type two pneumocytes with some macrophages. Increase in type two. Important, important, important. There's an increase in type two. Why? Because type two are the stem cells. So when there's so much destruction in type one, type two are like, "Hey, we can't leave our brother here. We got to help him out." So type two, the bigger brother. D is the bigger brother, right? So he's going to come and he's going to try to help, and he's just going to increase himself because this is a stem cell. It's going to try to produce type one pneumocytes. And you have an increase in fibroblasts. Fibroblast fibrosis. Where you see fibroblast fibrosis.
Complications of this pulmonary fibrosis or pulmonary hypertension, for sure. You have fibrosis, you're going to have hypertension, right? Because it's really hard for the, for it gets really hard to pump, and those pulmonary arteries thicken up and cause hypertension. Right heart failure because it's so hard to pump in there that this guy's going to fail. Right heart failure. Remember, and it's going to cause arrhythmias, choreic disease, respiratory failure, lung cancer.
Okay, so let's just recall the whole thing and see if we have anything important. This is very high yield that you have low type one, increase in type two, and increase in fibroblasts. Some of the, some of the, so when you have this persistent inflammation, right, that you're going to release some cytokines. What cytokines are you going to release? TGF-beta. TGF-beta. TGF-beta. You're going to also release platelet-derived growth factor, fibroblast growth factor, and you're going to release vascular endothelial growth factor. So why am I writing all that? Because for the treatment purposes, we're giving, we will give each one of them. We will try to inhibit that. So we will inhibit this TGF-beta by giving the drug known as pirfenidone. I'm going to write here, P-I-R-F-E-N-I-D-O-N-E. Pirfenidone. What is pirfenidone? It is the inhibitor of TGF-beta. It is basically anti-fibrotic. So this guy was causing fibrosis, we give pirfenidone, which is anti-fibrotic. That's one thing. And all the other ones, these right here, PDGF, FGF, VEGF, these side, these ones, they will be inhibited by, let me write the drug. So you can write too. So it is the N, is it Nintendo? N, I guess. Nintendo. Let me write N-I-B or something like this. Okay, I'll make sure what it is and then I can send it to you. You guys have any question on this one?
Okay, so what is this going to do? It's just going to inhibit all of these other factors. And why are we giving this drug anyway? Right? Because this drug will slow the progression of fibrosis. It's just going to slow the progression. Slows the progression. Slows the progression of fibrosis. And why was, why would, how would it slow the progression? Like all of these factors, what are they going to cause? Well, all of these factors are going to cause increased fibrotic activity, one thing, collagen production, second thing, and myofibroblast formation. These all things eventually will cause pulmonary fibrosis. We try to stop that, right? We try to stop that by giving this drug, drug which is called Nintedanib or something. And I will look into that and tell you what it is specifically.
Okay, so this is how, an important one. Other than this, yeah, so that's pretty much all for idiopathic pulmonary fibrosis, which is a summary, which is basically progressive lung disease without any cause because of there is a persistent lung injury, inflammation, fibrosis. And you just have, you just have on the PFTs, you will have reticular opacities, honeycomb appearance in advanced diseases. Interstitial pneumonia will be there. Importantly, decreased type one, increased type two, and increased fibroblasts. Complications, high yield, pulmonary hypertension, right heart failure, arrhythmias, choreic disease, failure, lung failure, fibrosis.
Now, the next one is hypersensitivity pneumonitis. Hypersensitivity, as you can see with the name, and itis is inflammation. It is a mixed type two hypersensitivity, which type two and three? Two, three? No, I mean, my bad, three and four. Three, four hypersensitivity reaction to environmental antigens such as thermophilic actinomycetes and Aspergillus, often seen in farmers and bird fanciers. Where? Farmers, bird fanciers. Acutely, it can cause dyspnea, cough, chest tightness, fever, headache. Often self-limited if stimulus is removed. Chronically leads to irreversible fibrosis with non-caseating granulomas, alveolar septal thickening, traction bronchiectasis.
Okay, so again, what is all this about? This is all about that you have so much destruction that it causes thickening, non-caseating granulomas with type three and type four hypersensitivity reaction, right? With the birds. So important thing in the history, you have farmer, the bird, the person who has the birds, that can develop all of these. So they will ask you what sort of cells are in type three, type four hypersensitivity reaction which are causing all this damage? They are your increased CD8 positive T cells, cytotoxic positive T cells are increased. High yield point. And that causes lymphocytic infiltration plus non-caseating granulomas and alveolar septal fibrosis with traction bronchiectasis. You're going to call hypersensitivity pneumonitis.