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Transplant is not a huge topic on the outside, but you're guaranteed to get a couple questions, so it's definitely worth reviewing. We've tried to distill it down to the highest yield as possible. We hope you're enjoying the podcast companion. If you haven't checked it out yet, check it out on Amazon. There's a link down below. Still time to get it in time for the app site. There's also the electronic version, so you'll get it immediately.
Thank you all for all your support and good luck studying. So I'm here with Jason and Megan and Jason is going to take us through transplant. So take it away, Jason. All right, let's get right into it. So let's just go through some basics of transplant. So Megan, so we talked about warm ischemia time and cold ischemia time. What do we mean by that and why does it matter?
So warm ischemia time is two periods. It's prior to organ removal from the body when it's thermothermic and it's also the period after the cold preservation before reperfusion. Cold ischemia time is that period from the time of cooling the organ to removal from the cold preservation solution. Most importantly, though, is that reperfusion time. So after cold ischemia, when the organ is revascularized, the majority of injury occurs during this time, and it's this ischemia reperfusion injury.
Exactly. Yeah. So it's important to know that distinction between the warm and cold. But I think where the question is going to be is when does that ischemia reperfusion injury happen? And that's after cold ischemia time when the organ is revascularized.
all right so megan we're gonna stick with you on this one so there's some different options for uh for cold preservation of organs and there's some different uh preservation solutions what are the different intercellular preservation solutions And how they work. So there's three solutions that. are named and out there. One is called Ural Collins. One is called histidine, tryptophan, ketoglutarate, or HTK. And then the one that we hear about the most is University of Wisconsin Solution.
These all provide electrolytes that reduce cellular swelling during preservation time. And notably the University of Wisconsin solution due to what it's composed of allows extended preservation of both the liver and pancreas. Great. Yeah. So, yeah, I don't see this showing up too much on the app side, the different preservation solutions, but it's good to have a general idea of how they work. And then, you know, there's also simple cold storage, which is more straightforward and less expensive.
and then there's some different you know products out there for pulsatile machines which have been shown to lower the incidence of delayed graft function for kidneys but just having a general idea of how organs are preserved so moving on kevin During organ procurement, aberrant anatomy is often encountered. What are some of the most common aberrant anatomy that we need to know when talking about transplant? Yeah, so this is important both for transplant and kind of.
other specialties such as vascular when performing procedures on these organs so for the kidney you always want to look for multiple renal arteries you have to check that ct scan because that can change how you reconstruct things and make the procedure more complicated I think it's close to 10% of kidneys will have multiple renal arteries. Sometimes the lower pole of the right renal artery will pass in front of the IVC rather than behind it.
And then the other thing you have to look out for is a retro aortic left renal vein. And this is especially important in vascular for when you're clamping the aorta. You can cause massive bleeding from a retro aortic left renal vein by clamping the aorta and not recognizing that the renal vein is behind the aorta rather than anterior where it normally lies.
Perfect. And I think the question that's going to show up is going to be what's the most common. And for kidney, it's multiple arteries. But absolutely, there's this other important variance that you need to know about. Okay, how about liver? For the liver, the most common is the aberrant right hepatic artery arising from the SMA. So rather than coming off the celiac as a branch of the celiac, your right hepatic comes off the SMA.
And this is important both in transplant and also in just doing a common bile duct exploration, et cetera, because you can damage that right hepatic artery if it's not visualized appropriately. or even a cholecystectomy it's important for even just your standard cholecystectomy that's a question that shows up a lot is what's the most
common anatomic variant there, and it's the aberrant right hepatic artery. And where does it originate from? The SMA. OK, how about let's keep going about the aberrant anatomy of the pancreas. Yeah, for the pancreas.
you know it has multiple different embryologic uh things that can happen it could be an angular pancreas you can have a pre-duodenal portal vein rather than the portal vein being behind the duodenum and then you can have a duplication of the portal vein and actually sometimes there's an absence of portal vein Okay, so now we're going to talk about some different types of donors.
We know there's living donors, there's brain dead donors, and then there's circulatory determination of death donors. And we'll talk a little bit more about what that means in a little bit. But let's let's start for with just some living donors. So Megan. contraindications to organ donation for living donors. What are some absolute contraindications?
so absolute contraindications are hiv and hepatitis infection although if the recipient is positive it is not a contraindication cirrhosis active systemic infection with positive blood cultures, and then melanoma, even if it's indolent for many years because this can end up showing up in organs and they can have mets that you don't know about.
Yeah, good. And I agree with you. I think that, you know, HIV historically has been an absolute conjugation, but more recently, especially for renal transplants, there have been HIV. positive donor to an HIV positive recipient has become more common. Now, how about some potential contraindications? So potentially, if the donor has a UTI, if they have a urosepsis, it's a contraindication. But if they just have a plain, simple UTI, they can still be a donor.
If they have low-grade visceral malignancies, it's a case-by-case basis whether or not they can be a donor. They also can still be a donor if they have a low grade brain tumor, such as a glioblastoma. And finally, if they have a history of abdominal surgery for a benign disease, they can still be a donor.
uh kevin so staying with living donor so uh living donor hepatic So, you know, indications for transplant are the same as deceased donor transplant, but there are some contradictions for a living donor for liver. So these patients generally have to be very healthy in order to give up half of their liver or however much it is.
So they can't have advanced cardiopulmonary disease. They can't have any primary liver pathology. They can't have any communicable infections or active or recent cancer history. And then there's, of course, a lot of anatomic restraints that has to be, you know, ideal situation because it's such a high risk surgery donating your liver. If there's multiple hepatic arteries, if there's aberrant biliary anatomy or insufficient residual liver volume, all of these can be potential contraindications.
Okay, great. And along the lines of that anatomy, for a living donor, what are some possible living donor graphs? What segments do they procure? So they can use the right lobe of the liver, which is segments five through seven. They can use the left lobe of the liver, which is two through four. Or sometimes they can just go with the left lateral, which is generally two and three.
Yeah. So you mentioned that. Perfect. That was great. But you mentioned that these donors have to be relatively healthy. What are some potential complications for the donor? So.
They can get infections. They have bile leaks, incisional hernias. If they have a small residual liver volume, it can lead to liver failure, which is one of the most dreaded, obviously. And then there's any kind of vascular complications, whether it's thrombus in the ivc and then you know unfortunately some of these patients die there's a multi-organ failure and death or risks of being a living donor
Exactly. So the complications are real and can be incredibly morbid. That's why you need a pretty healthy donor. They need to know what they're signing up for. How about follow-up for donors? So generally daily labs for three to four days and they'll get a post-op hepatic duplex. And then if there's a concern for a leak, they may end up getting a HIDA scan, but otherwise kind of routine outpatient follow-up once they're discharged.
Great. So, Megan, we're going to move on to a living donor nephrectomy. It's your living donor, kidney donor. So when we're talking about a living donor versus a deceased donor kidney transplant, what are the respective outcomes for those? So this is something where they do, I've seen questions on this where living donors actually have improved outcomes. So the recipient outcomes in both patient and graft survival are better with a living donor kidney.
They also spend less time on the waiting list and you can also because of that less time on the waiting list they can possibly have a preemptive transplant and avoid dialysis altogether. Yeah, exactly. And I agree with you 100%. That's a very testable question. I've seen that showing up several times. We talked a little bit about general contraindications. What about some contraindications for a living donor?
So for nephrectomies, if they have active or an incompletely treated malignancy, if they have an active infection, especially for kidneys, if they have diabetes or uncontrolled hypertension, these would be absolute contraindications. There's also some relative contraindications. So if they have a chronic illness or poor functional status, they wouldn't be able to handle having a single kidney. If they have impaired renal function, obviously recurrent kidney stones.
If they have controlled hypertension, that's debatable. And then if they have a history of treated malignancy, obviously if they're ABO or HLA incompatible, and then another relative contraindication is pregnancy. Okay, great. And how do you follow these patients, the donors? How do you follow the donor patients postoperatively?
so they actually have need a little more follow-up than the liver so they get blood pressure bmi creatinine glomerular filtration rate urine albumin all checked at discharge or six weeks post-op and again at six months, again at one year, and then finally at two years follow up. Perfect. How do you counsel these patients? What are some potential post-op complications to donating to kidney?
so commonly for them gi issues getting constipation there can be some bleeding complications or respiratory distress and then the standard complications that are related to surgery and anesthesia Okay, so that's a quick run through of living donors. So let's move on to that next category, which is that donation after brain death. First off, Kevin.
This is something you might run into when you're on, let's say, your trauma rotation. But what are the diagnostic criteria for brain death? How do you pronounce somebody brain dead? OK, so the diagnostic criteria for brain death. So you need clinical or neuroimaging evidence of a CNS. central nervous system catastrophe, the biggest thing is you have to exclude complicating medical conditions.
They can't have any drug intoxication. They have to be normothermic with a blood pressure systolic over 100. On a neuro exam, you would have an absent motor response, an absent pupillary light reflex, no corneal reflex. You have to check the oculovestibular reflex, known as doll eye. A jaw jerk test, they can't have a gag. Cough with tracheal suctioning.
or the sucking and rooting reflexes and they have to be apneic yeah so they do talk about the apneic test so yeah absent of all your basically your brain stem reflexes um and then a positive apne test So let's say now you have somebody that's brain dead and you're trying to get them to transplants. That can oftentimes be very difficult because these patients are a lot of times are...
very physiologically unstable. Megan, what are the common physiologic disturbances seen in brain individuals that need to be aggressively managed as you're trying to bridge them to transplant? So they obviously need to maintain their tissue perfusion so that their organs are retrievable and usable. They can get hypernatremia, so correcting that hypernatremia is important. If they develop diabetes insipidus, that needs to be treated. Of course, maintaining their oxygenation and ventilation.
If you need to provide ionotropic support, that may be necessary. And then preventing hypothermia, which is all, again, to maintain the organs until retrieval. Yeah, I mean, you think, you know, the patient's brain dead, but they became, they actually become very, it becomes very labor intensive just to keep them, you know, in a physiological homeostasis to work. they'll be eligible to donate and getting them to that transplant can be very difficult.
Okay, so we talked about our living donor. We talked about our donation after brain death. Now we're going to move on to that third category called the donation after circulatory determination of death. so kevin uh what are the criteria for donation after circulatory determination of death Yes, it's a little more complicated. These are patients that have no hope of viable recovery, many times a massive stroke, cardiac arrest.
multiple trauma, and the decision is made to withdraw life support. And so they're expected to expire within 60 minutes of withdrawing this life support. So the organ procurement can start two minutes after the patient is dead. But if the patient doesn't expire after the removal of that support within 60 minutes, they're no longer an organ donor.
Okay. Well, how about outcomes? What do you know about outcomes after donation after brain death versus the donation after circulatory determination of death? Interestingly, for kidneys, donors after circulatory death have equivalent outcomes to brain death donors. But for livers, they've shown that donors after circulatory death have a higher incidence of biliary complications.
Okay Megan, so now we're ready to go forward with transplants. So what's important in the workup of the donor and the recipient for a transplant? So they get an extensive workup in order to make sure that they match and to prevent rejection. So the first thing is performing the cross match. which is looking for preformed antibodies against the new organ. This is done by mixing the serum of the recipient with donor lymphocytes.
If that's positive, they are at risk for hyper acute rejection, which we'll talk about later. And then if their cross match is OK, I guess Jason throw it back to you. How would you test for HLA mismatch?
Okay, so for HLA Image Mesh, you need the... panel of reactive antibody formed against precipitous antibodies for HLA and you get what the PRA so the PRA is greater than 50% that's a contraindication of transplant so PRA greater than 50% contraindication transplant Things that can increase this are transfusions, pregnancy, previous transplants, autoimmune diseases. and currently plasmapheresis is being investigated as a way to treat sensitized individuals prior to transplants.
And I think this topic that we're discussing right here is a guaranteed question. And specifically, I've seen on question banks and the test. How do you perform across that? And so it's really important to know that you mix the serum of the recipient with the donor lymphocyte. And I think that's a very common question.
Yeah, it shows up pretty often, as well as the different types of rejection. Those are very testable things, so be sure you have those down. Those are easy points to miss. So, okay, let's move on to liver transplantation. When we talk about liver transplantation, we spend a lot of time talking about MELD score. So Kevin, what are the components of a MELD score and what's the minimum score you need to be considered for liver transplantation?
So its components is INR, bilirubin, and creatinine. 15 is the minimum score. And then you refer to a hepatologist to get them kind of on the transplant list once they hit a meld of around 10. Right, so 15 is the number, the very important number that calls you for transplant that's been shown at that number, you know, your survival is better with transplant. So there are some exceptions, however, that will just automatically give you a score of 22. And Megan, what is that exception?
So the exceptions that give you an automatic score of 22 are hepatocellular carcinoma within the Milan criteria, Heiler cholangiocarcinoma, hepatic artery thrombosis, and hepatopulmonary syndrome.
okay you mentioned the milan criteria what is it what is that exactly what's the milan criteria So that's where people with hepatocellular carcinoma, if they have one lesion between two to five centimeters, two to three lesions that are less than three centimeters or no vascular invasion they meet the criteria to get a hepatic transplant and so they get their score of 22.
okay i'm just going to repeat all this to go over this all real quick again because this is all highly testable things so meld score made up the pt-inr bilirubin creatinine 15 is that number uh that's the cutoff for uh transplantation although there are some exceptions. So hepatocellular carcinoma with Milan criteria.
hyaluric cholangiocarcinoma, hepatic artery thrombosis, and hepatic pulmonary syndrome, with the Milan criteria being one lesion between two and five, two to three lesions less than three, and no vascular invasion. Perfect. Contraindications to liver transplantation, Kevin.
So, you know, this is a big surgery they're going to undergo, so they have to be somewhat stable. So if they have insufficient cardiopulmonary stability, if they have active sepsis, if they have an uncontrolled extra hepatic malignancy, if they're still abusing substances such as alcohol, if they have a lack of social support or a recent intracranial hemorrhage. What about hepatitis? So hepatitis is not a contraindication.
Generally, hep C is known to reinfect the new liver allograft, but with new medications that can be controlled. And then hep B, you can give the hepatitis B immunoglobulin. Limiting to prevent reinfection. Okay, so let's talk about complications after a liver transplantation. So what are some complications that require going back to the operating room?
So going back to the operating room, if it's a primary non-function and the risk for this is a patient that has a kind of fatty liver, macrosteotosis is a risk factor for this. That's very nice. I see that question. I've seen that question happen a lot. So what is a predictor or risk factor for primary non-function? And the answer is macrosteotosis. That shows up pretty commonly. Sorry to interrupt, but go ahead. Other complications required.
take back to the operating room after liver transplant. So the post-op hemorrhage is an obvious complication, hepatic artery stenosis. can generally be treated with a stent but can potentially need a revision of anastomosis. And then one of the most dreaded complications is the hepatic artery thrombosis. And what do you do for that? So if it's early hepatic cardiothrombosis, you can, you know, fix it if it's identified early. But many times these patients need to be emergently re-transplanted.
Okay. And what about if it's late? If it's late, generally, they'll kind of show up with biliary strictures and abscesses due to the lack of blood flow. And so... then you can potentially attempt endovascular management of this versus potential retransplant. Sorry, I've seen multiple questions about a patient presenting after hepatic transplant with an abscess, and they want you to draw that connection between hepatic artery thrombosis and abscess formation.
Absolutely, absolutely. Okay, there's a few more other complications out there, Kevin. Yeah, so you can have a portal vein stenosis or thrombosis. This will generally present early. If it does present early, it will present with abdominal pain. Late, these patients may have upper GI bleed. Ascites is another. effect of this portal vein thrombosis treatment for this if it's early you should do a thrombectomy and revise the anastomosis.
Okay, so you can have IVC stenosis or thrombosis from re-implanting the liver on that, and that can lead to edema, ascites, renal insufficiency. The treatment for this generally is if it's far enough out from surgery, potentially thrombolytics, anticoagulation, and potentially an IVC stent. And then you can have early allograft dysfunction in these liver transplants.
Okay. Yeah, so those are all the complications that may require a return to the operating room. And then there are still some more complications that can generally be managed non-operatively. Kevin, we're going to stick with you. What are we talking about with those? So the bile leak is the most common complication and generally this can be managed with placing a percutaneous drain and stent open with an ERCP.
And then cholangitis is a kind of subsequent complication and these you can treat with antibiotics. Yeah, and as Megan has said, the way these typically show up in a board or a testing scenario is they'll give you the complication or they'll give you how the patient is presenting and they'll ask you what the underlying complication is.
generally what they're going for is that is that either that hempatic artery thrombosis the early versus late as megana said the patients shows up with abscesses they're asking you what's going on another common one is that bile leak restricture
So a lot of these questions just have to do with they give you a patient that's post transplant and they're having a problem and they're asking what the underlying physiology is. OK, so let's move on out of liver transplant and we'll move on to a real transplant. So Megan, how are real transplants? How are these technically? How are they done? So these are most commonly done through a retroperitoneal approach where you attach the donor kidney to the iliac vessels of the recipient.
Yeah, so you're putting them in the pelvis, you're reattaching them to iliac vessels. How about some technical nuances, some technical complications that can occur? What are the most common? So kind of thinking parallel to the liver, you can get renal artery and vein thromboses. So these you would want to diagnose by an ultrasound immediately when you have suspicion. And sometimes you may see proteinuria, which would be an indication of a renal vein thrombosis.
and then you want to treat this with a PTA and stent. ureteral stenosis and leak from that anasmosis and urine leak is actually the most common complication after kidney transplant and the treatment for this is a percutaneous drain and ureteral stenting. And then there's one other complication, which is a lymphocele, which usually presents as external compression of the ureter. This most commonly occurs three weeks after transplant.
showing up with decreased urine output, hydronephrosis, and fluid collection due to that external compression. And this can also be treated with percutaneous drainage, but sometimes that fails and you need to create a peritoneal window to allow drainage. Great. OK, he touched on this a little bit, but some complications, common complications in the post-op period after a renal transplant.
So you can see all urea due to acute tubular necrosis. There may be excessive diuresis due to urea and glucose. Some patients may develop diabetes due to the immunosuppressive medications that are used for the renal transplant. So Kevin, the way I see this show up a lot of times on the outside of the boards is it will give you a patient that's post-op from a real transplant and they're not making urine.
And a lot of times I'll ask you, you know, what's the best next step for evaluation? So what do you think? Somebody who's in an early post-op period not making urine from a renal transplant, what do you want to do? This is a STAT ultrasound. This can tell you both if the artery is open, if the vein is open, or if there's some sort of leak or a hydronephrosis presenting.
Yeah, so yeah, renal ultrasound gives you a lot of information. So again, you can evaluate that renal artery or vein for thrombosis. You can look for a uranoma, you can look for a lymphocele that's maybe causing some compression. And generally, that's what they're looking for with that next best step.
Okay, so we covered liver, we covered kidney. We're going to cover some of the one that we may not have as much familiarity with or see as much, at least I didn't in residency, and that's the pancreas transplant. So Megan, who is a candidate for pancreas transplantation. So most commonly the people who get pancreas transplantation are those with diabetes with renal failure.
Okay, diabetes with renal failure, perfect. There's three different kinds of renal, I'm sorry, three kinds of pancreas transplants. What are those? So you can do a pancreas transplant alone, you can do a pancreas transplant after kidney transplant, or you can do the simultaneous kidney and pancreas. Right, exactly. Kevin, what's a vascular, you're a vascular surgeon, what types of, what are the arteries and veins you need for a pancreas transplant?
So you need the donor celiac artery and you also need the SMA for the arterial supply to implant into the patient and you also need the donor portal vein for drainage. perfect so you need the donor celiac sma and portal vein um what are the different operative methods kevin So they have a couple different ways of implanting these. They can do enteric drained. where the pancreas it drains and is an estymose to bowel and that is how you get the pancreatic enzyme
Or you can do bladder drained, where they plug the pancreas directly into the bladder. And then you can also do venous drained or portal drainage. What's the most common? Systemic drainage is the most common, but the portal vein drainage has not shown any advantage. Yes, the most common systemic venous drainage is what happens here with these pancreas transplants.
Okay, Kevin, you mentioned some, you know, enteric bladder, enteric versus bladder drains. What's the most common there and what's the advantage of that? So most anastomose to the small bowel versus the bladder, the advantage of draining to the bladder is the ability to monitor the amylase in the urine, but this has long-term complications of strictures and leaks.
Perfect. Okay. Megan, when we talk about, you know, what are the different comorbidities associated with the diabetes that can be ameliorated after a pancreas transplantation? So a lot of comorbidities with diabetes and renal failure, so retinopathy, it may not be reversed or improved, but it'll at least stabilize after a pancreas transplant.
The neuropathy will stabilize and can even improve. Pancreas transplant also protects kidney transplants from recurrent diabetic nephropathy, so it's renal protective. consistently have a benefit and quality of life. The one thing that is not going to get better is the vascular disease which continues to progress. Okay, great. Complications, Megan.
So you can get allograft venous thrombosis, which is very difficult to treat. And then rejection and in pancreas transplant rejection, you'll see increased glucose or amylase. or leukocytosis and it tends to be hard to diagnose if the patient does not have a simultaneous kidney transplant. Okay and is there a mortality benefit for pancreas transplants or is it purely the quality of life?
so the benefit in mortality is when they also have a kidney transplant because the benefit is actually from the kidney transplant yeah yeah so the benefit of mortality is from the kidney transplant and then went to again just to rehash those comorbidities so you know it'll stabilize retinopathy it'll stabilize your neuropathy potentially improve your neuropathy the real advantage here that was it protects the kidney transplant from recurrent diabetic nephropathy
And again, your vascular disease is going to progress. OK, so we covered liver, we covered kidney, we covered pancreas. now let's go on to talk about immunosuppression and of all the transplant this is probably the most highly tested most and highest yield so um so make it up When we talk about rejection, what cell lines are responsible for each type of rejection, what is a treatment? Let's start with the hyperacute, so hyperacute rejection. Tell us a little bit about that.
this is something i have to review every year for ab sites i spend a lot of time on it so hyperacute rejection occurs within minutes to hours and this is due to that abo mismatch So it's the preformed antibodies against the donor lymphocytes, which is also a type 2 hypersensitivity reaction.
Exactly. So let's say this, you know, this happens. What do you see interoperatively? Let's say, well, if you're doing a kidney transplant and they have a hyperacute rejection, what's, how's that going to present in the OR? So you would see the organ immediately becoming modeled. It'll turn purple, become soft, and then in a kidney transplant, it would demonstrate decreased urine output.
and what do you do what's the treatment you have to re-transplant them unfortunate yeah unfortunately re-transplantation so again these are very highly uh very high yield very highly testable hyper acute minutes to hours it's from an abl mismatch Again, it's preformed antibodies from lymphocytes. And it's a type 2 hypersensitivity reaction. It presents interoperatively modeled purple organ. I need to retransplant. Okay, Kevin, acute transplant. How does that present?
So acute rejection, this occurs a little more delayed. This is weeks to about one month out from surgery. And this is from cytoxic helper T cells. Okay. How about in the kidney? How does an acute rejection present? So generally, the creatinine will rise approximately one month after the transplant. your ultrasound will show a normal duplex. It'll have normal inflow and outflow and no lymphocele, but you'll end up getting a biopsy of the kidney and that'll show tubulitis.
and these patients will generally have decreased urine output. Okay, and... The patients will also, you know, kind of note some tenderness from the graft side. They may have some fevers and generalized feelings of just feeling unwell and malay. And you'll see, again, as you kind of mentioned, elevated serum creatinine and leukocytosis can also be seen. Okay, how about acute rejection with a liver? Tell me a little bit about that.
So once again, this is T cell mediated and these T cells are attacking the blood vessels in the liver. So these patients will present with the same kind of fever. They may have jaundice. They may have decreased bile output. And then with your labs, you're going to see a leukocytosis. You're going to see eosinophilia, increased LFTs, and total bilirubin, along with increased PT or INR.
And then on the path for this, once you get your liver biopsy, you'll show portal, triad, lymphocytosis, and then endotheliitis, and then bile duct injury. Okay, and how do you treat these patients? So both for kidneys and livers, acute rejection, which is weeks to a month after you're going to increase their immunosuppression, generally kind of a steroid. Okay, again, so acute rejection weeks to months, it's T cell mediated.
We went over a little bit on how you, what you can see in a kidney and a liver. The treatment is increased immunosuppression and what the addition of steroids. Okay, Megan, so chronic rejection. How does that present and what is that mediated by? Rejection occurs months to years post transplantation mediated by both the B and T cells. And this eventually leads to graft failure. It is a type four hypersensitivity reaction.
Great. So months, years, B, anti-cell, graft failure, type IV hypersensitive reaction. What do we see with these various organs? So how does it present after a liver transplant? So this is a common question, too, where the patient has disappearing the vanishing bile ducts. You can also see an increase in their ALKFOS and portal fibrosis.
Yeah, exactly. It'll disappear in bile ducts. OK, how about lung? There's a very kind of a path. I'm not going to say path mnemonic, but at least in the test taking it is. How does this present after lung transplants, especially on a board exam? Yeah, so the words to remember, bronchiolitis obliterans. Exactly. Bronchiolitis obliterans after lung transplant, chronic rejection treatment.
So again, you would increase their immunosuppression, but because this has been chronic, they will eventually need a retransplantation. OK, and then there's. something called chronic allograft vasculopathy. Kevin, again, this is a vascular thing, so I'll go back to you. Tell us about that. So this will be chronic rejection of the blood vessels resulting in fibrosis. Most commonly it is seen in cardiac transplant patients and the treatment for this is steroids and eventually re-transplant.
So let's talk about our natural killer cells. So how do these work? They identify cells by expression of what? So natural killer cells, they use the major histocompatibility complexes. So MHC class 1, it's present on all of the nucleated cells. Binding of the CD8 T cell receptors to MHC class 1 triggers the APC to undergo death via cell apoptosis. So this is why natural killer cells are associated with cell death.
Perfect. So CDAT cells receptor to MHC class 1 and death via apoptosis. I've seen that actually as what is the mechanism of death after this interaction is apoptosis. So natural killer cells are actually inhibited by MHC class 1. So if a cell does not express that, it will be destroyed by the natural killer cells. So this is your innate immunity. So Kevin, we're talking about MHC class one. What are the three MHC class one expression?
So you have HLA-A, HLA-B, and HLA-C. What's an easy way of remembering that? So one letter for MHC class 1 versus two letters for class 2. Okay, so what are keep going with that so I may chase MHC class to what are what are these? Where are they located? So these are the antigen presenting cells. This complex presents antigens to the helper T cells that express the CD4 receptor. So binding of the CD4 receptor, yeah. Click on.
So binding of the CD4 receptor to the MHC2 complexes primes the naive helper T cells and polarizes the cell to become either a memory T cell or an effector T cell. right another way i kind of remember that interaction is everything it should when you uh multiply those numbers it should add up to eight so mhc class two with cd four two times four is eight I'm actually class one with CDA, one times eight is equal to eight. Maybe that helps you, maybe that doesn't, but it helps me.
So antigen presenting cells, what do they do and where do they come from? So these bring phagocytized material to the thymus and lymphocytes to assist in cell mediated immunity. OK, so we talked about MHC class one being HLA, A, B and C. What is MHC class two? What are those HLAs? So it's HLA, DP, DQ and DR. Okay, so... Gracias.
So the question may say something like, which of these MHC class II molecule, and you'll see the two-layer HLA. And these are the most important for matching a donor and a recipient. Okay, moving on into immunosuppressive drugs. Again, another very high yield and topic that everybody always has to review prior to the outside. So what are the three classes of drugs to prevent rejection, Megan? The three classes are the induction agents, the antiproliferatives, and then the calcineurin inhibitors.
Okay, so tell us a little bit first off about those induction medications. What are they used and what are the more common induction medication? So the induction agents are used immediately postoperatively to prime the patient. In some of the induction regimens, they actually also deplete T cells and the medications for that are monoclonal antibodies. that bind to the IL-2 receptor of the T cells to impair their proliferation. So that is, and pardon my pronunciation, daclizumab and basiliximab.
So those are the T-cell depleting induction agents. And then in addition, patients are typically given steroids for induction. And remember that steroids inhibit IL-1, IL-6, and macrophages. Steroids are also used throughout transplantation, both induction, maintenance, and for rejection as we described. And then the other one used is antithymocyte globulin.
You may have heard this as thymoglobulin, which is a rabbit polyclonal antibody against the T-cell antigens, or the ATGAM or ATGAM, which is an equine polyclonal antibody. And these are against T-cells CD2, CD3, and CD4. So thymoglobulin is used as an induction agent, and it can also be used for acute rejection. Excellent. So yeah, those are induction agents. So you have your.
monoclonal antibodies, which you pronounce beautifully. I'm not going to even try to repeat those. I have trouble with those. Your steroids and then your antithymocyclobulins. Again, we're talking a new class of induction age. Kevin so the next class is anti-proliferative what are our anti-proliferative drugs how do they work what are the side effects
So mycophenolate and azathioprine are the main antiproliferative medications. So for mycophenolate, also known as NMF or Cellcept, it inhibits de novo purine synthesis, which inhibits growth of T cells. There can be many side effects of this. The main one with mycophenolate is GI intolerance. And then you can have myelosuppression and then you can also have CMV infections. But this is a good maintenance therapy.
And for azathioprine, the mechanism is also a purine antagonist. And that's how it works. Yeah, so antiproliferative, you know, the salsept or mycophenolate inhibits de novo purine synthesis and then azothyropine is a purine antagonist. As Kevin mentioned, a side effect most common is GI intolerance. Okay, Megan, moving back to that third class, those calcineurin inhibitors. What are our different calcineurin inhibitors and how do they work?
I feel like I see these questions most commonly for the immunosuppressive. So there's cyclosporine, tacrolimus, and serolimus. Cyclosporin binds to the cyclophylline protein that then goes and inhibits calcineurin, which causes a decrease in IL-2 and IL-4. This is also used as a maintenance immunosuppressive. But the big thing is the adverse reactions. It causes nephrotoxicity, hepatotoxicity, you get tremors, seizures, and you can even get hemolytic uremic syndrome.
And then importantly, this is metabolized in the hepatic system and excreted in the bile. Yeah, so Kevin, cyclosporine, hepatic metabolism, bilary excretion, how does this show up on the test? So generally this would be a kidney transplant patient who presents an acute renal failure after getting a common bile duct exploration with a T-tube. and so their cyclosporine is being drained through the T-tube into their bag, their T-tube bag, and so they're not getting their immunosuppression.
Exactly. And that's exactly how this shows up. It's a classic question. And I'll give you somebody who had a kidney transplant. previously and now they've had a T tube placed. They won't even tell you what immunosuppressant they're on. They'll either ask you what's going on or they'll ask you what medication were they on? And so it's a cyclosporin. It's because of that and hepatic metabolism and the biliter.
Okay, sorry, Megan, I interrupted you. So that's cyclospora and a calcineurin inhibitor. You mentioned a couple other ones in there. How do they work? So tacrolimus or FK506 or prograph, this binds the FK binding protein, which then again goes to inhibit the calcineurin protein and again inhibits IL-2, IL-4 and interferon gamma. The side effects of this drug is nephrotoxicity, GI symptoms, you can get mood changes or diabetes.
And then sirolimus or rapamycin, it binds the FK binding protein, which then goes and inhibits mTOR, which blocks IL-2. Importantly with this, it's not nephrotoxic as versus cyclosporine and tacrolimus, but the side effect of this drug is interstitial lung disease. perfect okay um so those are your calcineurin inhibitors um so let's work on move on to uh infectious complications um after transplant so what are the becoming one of the most common infections
So CMV, the BK virus, and then PCP or pneumocystis, carnine, pneumonia. Okay. Respectively, how do those three different things present? So CMZ, the patients can have flu-like symptoms, they can have hepatitis, nephritis, lymphadenitis, leukopenia. And they may also have pneumonitis and GI symptoms such as gastritis, colitis, esophagitis, or bleeding peptic ulcers.
Okay. And then for the BK seen after renal transplant, they can present with ureteral stenosis and obstruction, and they can also have tubular interstitial nephritis and a rise in their serum creatinine. And then for the PCP pneumonia, they have hypoxia, dyspnea and coughing. The chest x-ray usually is normal, but CT will show diffuse interstitial infiltrates and nodular infiltrates. So how do we prevent these typical prophylaxis regimens given for these different pathogens?
So for PCP, they're on Bactrim daily for four to six months post transplant or lifelong in some circumstances. For CMV, If they underwent a T-cell depletion during induction, they're going to be on six months of an antiviral. If no T-cell depletion, they can be on just three months of an antiviral. then from you could to prevent mucocutaneous candida sometimes they're on oral
Glutrimazole or Nystatin BID. Perfect. OK, so those are your typical prophylaxis that you get post transplants to prevent some of those common post transplant infections. So let's talk about some long term. So we're going to stay with the theme of postoperative long term complications. So Megan, we touched on this earlier actually, but first step in evaluating postoperative kidney and liver dysfunction, and what are you looking for with each of them?
What's the first step? We mentioned it before. You have somebody whose kidney's not working or the liver's not working post-op from a transplant. Yeah, so you want to get that ultrasound. Always remember to get the ultrasound as your first step. because in the kidney, like Kevin had mentioned, you can identify the arterial and venous flow. You can identify any fluid collections like a lymphocele or a urine leak and hydronephrosis of the kidney.
Similarly, in the liver, you can assess the portal venous flow, the hepatic arterial flow, hepatic venous flow, the patency of the IVC, and look for any intraductal biliary dilation. Right. Yeah, exactly. So ultrasound is extremely useful in post kidney and post liver transplants to kind of sort out what exactly is going on.
Okay, Kevin, how about delayed graft function? How does this present after kidney, liver, and pancreas transplant? Delayed graft function in these different organs, how does it present? Yeah, for the kidney, they'll generally present with oliguria or a requirement for dialysis within the first week after transplant. And then for the liver, you'll see AST and ALT increasing generally greater than 1,500 within 72 hours after the transplant.
And then for primary non-function in the first 24 hours, the ability is greater than 10 and the bile output decreases to less than 20 cc per 12 hours. or they have an increased inr ptt and uh and then after 96 hours they can actually get altered mental status even further increasing the lfts renal failure respiratory failure which and those patients are all headed towards what Retransplant. Yeah, those patients are all had a tortory transplant. Okay. Pancreas.
for pancreas, are they going to have high insulin requirements within the first week after transplant? Okay. Megan, what's the best test to follow in a liver transplant patient to determine the synthetic function of the liver long-term? That's going to be your PT or INR. It's the most helpful for liver function.
LFTs is a misnomer, so these liver function tests don't actually, so AST, ALT, they don't actually test the synthetic function of the liver, so it's more of a marker of inflammation or cell death. Exactly. So yeah, your liver function tests are not actually your liver function tests. For your function, you want to go to your INR or PT. Your PTT and albumin are also helpful.
And, you know, belly ribbon has too many extrinsic factors to really rely upon as a determinant of liver function. So INR, PT, maybe PTT, maybe albumin to test that synthetic function of your liver. Kevin, what is post-transplant lymphoproliferative disorder or PTLD? So this is related to the Epstein-Barr virus. These patients can present with a small bowel obstruction or mass or adenopathy.
And the risk factors for this are some of the immunosuppression that they're on. So if they're on a cytolytic drug, such as thymoglobin, this puts them at higher risk for these Epstein-Barr virus-related problems. You treat this with withdrawal of immunosuppression. And so it may be switching them over to something like rituximab. And they may need chemo or XRT if it is an aggressive form.
perfect okay so that's that's our general overview of transplant let's move on we'll finish up with our as always with our quick hits so Kevin number one and malignancy following any transplant common Squamous cell, skin cancer. Yeah, following any transplant, number one malignancy, squamous cell, skin cancer. Make it a most common cause of mortality after kidney transplant.
It's MI. Yeah, MI, mortality after kidney transplant, most common. Kevin, most common reason for indication for liver transplants in adults. hepatitis C. Great. Megan, who has power of attorney of a brain dead patient who has no designated POA but has a girlfriend, a sister, and mother at the hospital all waiting to make decisions? The power of attorney in that situation is going to be the mother. So the order of this is the spouse, but in this situation there was no spouse.
adult child also not presented in the situation next up would be either parent and then finally as an adult sibling Yeah, and it's important to note that the questions are these should always be are always allow the procurement agency to make contact to have these discussions.
i've seen this question as irritating as it is this question does show up on the boards so you kind of do have to know that hierarchy and that's exactly how they'll give it you have a number of different people you have a girlfriend you have a cousin you have a sister, you have an adult child there who is able to make that decision. And I've even seen the question like who should have that initial conversation, the physician, the nurse.
the procurement agency. So those are simple questions to miss. So just make sure you know that stuff. Again, so as transplants, it's a small proportion of the outside, it's about 2%, but generally the questions are pretty straightforward. And if you have a general understanding of some of this transplant, particularly the drugs, the side effects.
and the post-op complications, you'll be able to pick up those extra 2% and that'll be the difference between your 80th percentile and your 98th percentile. So a small proportion, but important. So I hope everybody's studying is going well. So good luck and dominate the upside. Be sure to check out our website at www.behindthenife.org for more great content. You can also follow us on Twitter at Behind the Knife and Instagram at Behind the Knife Podcast.
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