Cirrhosis

Hey future doctors thanks for joining me on Spoonful of Sugar, a podcast made for medical students by medical students to help the medicine go down. My name is Rhea Mulherker. I'm currently a medicine intern in Philadelphia and I will be your host today. Welcome back team. I do want to thank you guys so much for continuing to tune in to Spoonful of Sugar. In the last couple of months we've actually had such an expansive growth in our following in terms of subscribers listeners and so on. And so I just want to thank you all for the support and the amazing feedback that we've received. You know this podcast was created with the intention to help medical students and so if there's anything additional that you would like us to do if there's anything that we can change about how we do these episodes we would love to get some feedback on that because I think it's paramount that what we do is helpful for you and I really do want to keep this as a free easily available resource for students to study especially with the weather getting nicer. I don't know what what part of the you know world you're from but I live in Northeast USA and spring time is here and it's been really really nice to get out and get some good weather. I'm hoping this podcast allows you to get out and get some good weather. I think we're also nearing that time of year where a lot of students have just finished taking step one or they're gearing up to take step one. I think I took step one in June so depending on what your school schedule is I know everything is mixed up you know with the COVID pandemic but regardless of where you are in the process of step one I think that today's episode would be a really great review not only to prepare for the exam but also to prepare for the wards and just kind of solidify your understanding of a very complex and interesting condition known as cirrhosis. That's right the topic of today's episode is cirrhosis and I think it's very applicable and important you know moving forward in your medical career. Not only is it super interesting to learn and study because it involves a ton of systemic effects there's a lot of interesting physiology involved not only in its manifestations but also its complications. It's a very common condition that you'll encounter in the hospital and management is very interesting it often involves a lot of very specialized hepatologists and there's you know different teams of doctors that handle patients with cirrhosis because the more cirrhosis progresses the more and more complicated it gets and it's just really important to have a good idea of what cirrhosis is what happens in patients who have cirrhosis and why it happens and then some complications of cirrhosis that are commonly seen in hospitals and can be really life threatening. And so that's exactly how I'm going to structure this episode. We're going to talk about the definition of cirrhosis, the pathophysiology and then we'll talk about the complications. As we go through I'll also touch on some management strategies and some of the key concerns that we see in patients with cirrhosis and the certain complications of cirrhosis. Again this is just to give you a broad overview I'm hoping it'll be really helpful for you in preparing for the boards but I also really hope that it'll be helpful for you in transitioning that knowledge from the textbook and pathophysiology alone to clinical presentation and application for the wards. So with that said let's get started and I'd like to start by asking you guys what is cirrhosis? So by definition cirrhosis is characterized by scarring of the liver. The stellate cells of the liver will undergo diffuse bridging fibrosis and then there are regenerative nodules that form and these regenerative nodules will actually disrupt the normal architecture of the liver. So it's a fibrosis process also known as scarring. What you should know about fibrosis and scarring these words refer to irreversible processes. Okay fibrosis is the tissue that is laid down kind of in response to chronic inflammation and unfortunately it just cannot be reversed. So what causes cirrhosis? Many things. Some of the most common causes include alcohol and nonalcoholic stiato hepatitis. So you'll hear that abbreviated as NASH or NASH cirrhosis. So there's alcohol just fatty so that's what stiato stiotosis refers to. There's viral hepatitis. There's autoimmune hepatitis. There's biliary diseases that can lead to cirrhosis and then there's also some genetic metabolic disorders which are rarely seen in the hospital but commonly tested on boards. So just to kind of quickly review some genetic metabolic disorders that can result in cirrhosis. What if a patient comes in, has chis or flusher rings in the eye and on their labs you see decreased cerule plasma. Wilson's disease very good. This is a defect in the copper transporter. Now what if there's another genetic disease and this patient has this triad of cirrhosis? Diabetes mellitus and their skin color is kind of bronze. They have a bronze pigmentation to their skin. Chemochromatosis is very good. So this is a defect in iron sensing and it actually causes increased iron absorption. So you get iron in the liver, cirrhosis, iron in the pancreas, diabetes and iron in the skin which causes bronze discoloration. And fun fact if you have enough iron in your body you can actually light up when you're passing through security at the airport. And then last one I want to review in terms of the genetic conditions. Let's say a young male comes in and he has liver damage but he also has dyspnea. No history of smoking, no alcohol. What am I going for here? Liver and lung in a young male with no other causative factors like smoking or alcohol. This is alpha-1 antitripsin deficiency. So what happens is you cannot break down elastase and in the lung you end up getting panacin or emphysema because there is breakdown of the actual alveoli because elastase is super active. So good job with those genetic metabolic diseases. Again I want to emphasize these are not commonly seen in clinic or in the hospital. The most common causes are usually alcohol or the non-alcoholic steatosis that I was talking about as well as viral hepatitis. But it's important to know these for the boards and it's good to be familiar with some of these rare conditions as well. Now why is cirrhosis so bad? So I kind of alluded to this before. The damage in cirrhosis is literally scar tissue and fibrosis and it cannot be reversed. So it can either be controlled or it can just worsen and worsen until patients get really really sick. And patients with cirrhosis do get really really sick and that brings me back to the very interesting pathophysiology of cirrhosis. The liver is a very key organ and so it makes so many different products and so when the liver is not working you get a ton of systemic effects as a result of that. And then there are the complications of cirrhosis which can be extremely life-threatening. And so we will be going over those as well. And finally having any kind of chronic inflammation anywhere in the body can increase your risk of cancer. So having inflammation that leads to fibrosis in the liver can increase your risk of developing hepatocelular carcinoma. And it's very common to see patients with cirrhosis who later develop hepatocelular carcinoma. So again everything I've just said cirrhosis can do very bad things. Now how does cirrhosis usually present? Like what would the patient look like? Just try to imagine them. So yellow if you're thinking of the word yellow or jaundice that's a very good thing to be thinking of. Once you've seen a single cirrhosis patient you won't forget what they look like because it is so striking. And if you're listening to this before you know any experience in the hospital that's totally fine. I'm just going to describe a typical case of you know cirrhosis presentation and emphasize some key findings that you would see. So let's say a 56 year old male with a history of diabetes, hypertension and alcohol abuse comes into his primary care physician because he has noticed some yellowing of his eyes. He's also complaining of some weight gain in his abdomen and he's having some abdominal discomfort more recently. His wife is with him and she says he's been acting really confused. When you go to do the exam he has sclerolictorists. His skin does appear diffusely jaundiced. He has palmar erythema and he also has some gynecomastia. Abdominal exam. His abdomen appears distended with some spider angiomas overlying his skin and on palpation you feel dullness to percussion as well as a palpable fluid wave. When you ask him to stick his hands out as if he's stopping traffic he has a flapping tremor of his hands. So that's just a Just a sample case of a patient with cirrhosis, and what I'd like to do now is break down the pathophysiology of all the various physical exam findings that I just saw. The first one, and the most obvious one I'd like to talk about, is jaundice. Why do patients with cirrhosis become yellow? So the liver, remember, one of its functions is to conjugate billi-rubin for excretion. So what ends up happening in cirrhosis is that the liver does not do that job, and so you end up getting an accumulation of indirect billi-rubin. Remember, heme is broken down in the blood and is formed into indirect billi-rubin, and then in the liver it gets conjugated to direct billi-rubin. So if your liver is not working, you get an accumulation of the indirect billi-rubin that's not conjugated, and it ends up accumulating in the body and causing jaundice. And just a fun little clinical fact, do you guys know where's the first place that we typically see jaundice? So I've been told that the first place is usually the pallet as well as the tongue, and then the sclera, and then the full body. So if you're suspecting that a patient has cirrhosis, but you don't really see any sclerolictoris or appreciate jaundice, you can always ask them to open up their mouth and look at their pallet and their tongue. So let's go on then to the next skin finding that I described. I described findings of palmar erythema and spider angiomas. Do you guys know why a person with cirrhosis would have this? So another function of the liver is to break down estrogen. So if the liver is not working, you get decreased breakdown of estrogen, and so it accumulates. And interestingly, estrogen is associated with these findings of palmar erythema as well as spider angiomas. Not only these, it also explains the gunnacle mastia, and sometimes in males you'll see testicular atrophy and women you'll see amenorrhea. The next finding I described was abdominal distension. I said the belly was very distended, there was a palpable fluid wave and dullness to percussion. Here all of these alluding to, acides, patients with cirrhosis will often, often often develop acides. And if you're seeing a belly for the first time on the wards and you've never seen somebody with acides, if the belly is very stiff, very, very distended, like usually even if a patient is obese, their belly is soft, patients with acides, the belly is super distended and the skin is taught over all of that fluid causing distension. So it takes a while to get used to what that exam looks like, but once you see it one or two times, again you won't forget it. So what is acides? Acides is an accumulation of fluid in the abdominal cavity. And sometimes patients with cirrhosis not only have fluid in their abdominal cavity, but it spreads everywhere in their body. And do you guys know what that's found when there's fluid just diffusely third spacing in the entire body? That's called anasarca. And just to clarify, when I say third spacing of fluid, I mean fluid going into the interstitial space. So most of the fluid in your body is either in the cells or in the vasculature. But third spacing of fluid refers to fluid in the interstitial space, so where it's not really supposed to be. So you get third spacing of fluid in the abdomen, causing acides. And then if it goes everywhere in the body, it's called anasarca. Now why would we see that? Why would we see third spacing of fluid everywhere? So another function of the liver is to make proteins such as albumin. Measuring the albumin level in patients with liver disease is really important because it tells you what the functional status of the liver is. So patients require albumin, well, all of us require albumin really to help uphold the oncotic pressure in our vessels and help keep fluid in the vessels. But if your liver is not making albumin, there's no albumin in the blood vessels. And then the oncotic pressure in your vasculature is very low. And it doesn't hold in the fluid anymore. The fluid just kind of seeps out into the third spaces, into the interstitial space. And so that's why we see acides and anasarca in patients with cirrhosis. Now you can imagine that losing all of that fluid from the blood vessels makes these patients kind of drop their blood pressures. And that's absolutely what you see. Serotic patients usually run on the hypotensive side, so it's not uncommon for these patients to live at 80 to 90 systolic blood pressures. Now, all this fluid in the belly obviously is uncomfortable. As I described in our case of the 56-year-old gentleman, it's painful and it's not comfortable. So one of the things that we can do to help relieve the pressure from the fluid is to perform a procedure called a parasintesis, where we literally just drain the fluid out using a little needle. Now, something to think about is that when you remove all that fluid, you're creating a fluid shift in the body. So where all that fluid just was, you're going to have more fluid in the blood vessels that wants to come out and replace it right away. So something important to consider is that when you are performing a parasintesis and draining acides from a person's belly, you need to measure how much you're draining. If you drain more than five liters of fluid, you want to make sure that you give back some IV albumin so that you can help support the oncotic pressure in patients with cirrhosis and prevent them from once again just start spacing all their fluid and dropping their blood pressures to a dangerously low level. I know that was kind of a complicated explanation, but I do think it's important to understand where acides comes from and potential complications of acides. And it is important to be familiar with the utility of parasintesis. It's not only therapeutic to relieve the discomfort, but it can also be diagnostic. And we'll talk about why you would get a parasintesis a little later for certain complications of cirrhosis. The final exam finding I want to tackle here is the flapping tremor that I described. What is the flapping tremor called? Do you guys know another medical word for that? Cerrhosis is really good. So a flapping tremor, also known as asteriscus, is a very pathonomonic finding in patients who have hepatic encephalopathy. And what causes hepatic encephalopathy? So it is thought to be due to a build-up of ammonia. Whenever you see a patient with cirrhosis, if they have a history of cirrhosis, always check for asteriscus. If you want to assess their mental status, see if they're confused, maybe ask them orientation questions. Do you know your name, where you are, what month it is? But then it's also important to check for asteriscus. And the way you do that is just ask patients to stick out both their arms like they're stopping traffic. So their palms should be sticking up kind of perpendicular to their arms. And if their fingers start to flap, that is a positive for asteriscus. And if you didn't understand what I just described, I would highly recommend googling a video of that. It's important to be familiar with asteriscus. Now I think the treatment of asteriscus is actually really cool. Do you guys know how it's treated, any idea? So like I said, asteriscus is thought to be an hepatic encephalopathy in general. It's thought to be due to a build-up of ammonia. So what we want to do is try and get rid of extra ammonia. So one of the treatments is lactolose. What lactolose does is it's converted to lactic acid and acetic acid in the colon. And it actually acidifies the colon. That causes ammonia to turn into ammonium because it gets that extra acid hydrogen adds on to the ammonia and makes it NH4+. So ammonium. And with that positive charge, it becomes trapped in the colon and it ends up getting excreted via stool. So usually you give lactolose to try and kind of cause osmotic diarrhea and keep the ammonia trapped as ammonium in the colon. And usually you give lactolose and you can titrate the dose to about two to three bowel movements per day to make sure patients are losing enough ammonium in their stool. And then some patients will be on lactolose alone, but some patients will additionally be on an antibiotic called refaxamin. Do you guys know what the utility of refaxamin is? So this is an antibiotic that actually decreases the ammonia producing bacteria in the colon. So it's kind of two ways at decreasing the levels of ammonia in the body, lactolose and refaxamin. So I know that was long, but I'm hoping that you guys kind of understand the breakdown of the different findings that we see in cirrhosis, as well as the pathophysiology and understand why these findings actually occur. Now let's spend a couple of minutes talking about labs. What would labs show in a patient with cirrhosis? So they can show signs of liver injury as well as liver failure, and it's really important to understand the difference between liver injury. and liver failure. So to assess for liver injury, we just measure the liver function tests. Okay? In patients with cirrhosis, you can get elevated transaminase levels, so AST and ALT. And elevated transaminase levels are more consistent with intrinsic renal injury, whereas remember that elevated ALP and GGT are more associated with some kind of obstructive process downstream of the liver. So you'll see elevated transaminases, consistent with intrinsic injury, and then you can also get the indirect bilirubinemia, which we talked about earlier. And then what tests would you do to check for liver failure, and how are they different from the labs for liver injury? So remember, liver failure means that the liver is not able to perform its synthetic function. So look for the things that the liver makes. One of them, which we kind of touched upon earlier, is albumin. So patients with liver failure will have low albumin levels. And what's usually a normal albumin, do you guys know? Four is typically normal, and patients with cirrhosis will often have albumin levels that are as low as one or two, so very low. And then what else does the liver make? Coagulation factor is very good. So you can definitely check some coags. You can check PT, PT, INR. Remember, INR is just kind of a surrogate measure of the PT, and it represents the extrinsic pathway of coagulation. So INR is typically high in patients with cirrhosis. And normal INR is one. Patients with cirrhosis, it's not uncommon. I've seen INR as high as five or six in patients with cirrhosis. So you can check for albumin, you can check for coagulation factors. And that tells you that if the liver is not synthesizing things correctly, you're in liver failure. So now then, let's move on to the best part I think of this episode, the complications of cirrhosis. I think the complications of cirrhosis are super interesting as well. So let's go back to our 56-year-old gentleman who presented into the clinic. What if the same man with the same sort of history instead of going to the clinic presented to the emergency room with hematemosis? He's like actively vomiting blood. What are you worried about? Esophageal varicies, very good. Varicial bleeding is a very common complication of what condition do you guys know? Portal hypertension, great. So let me start by talking about portal hypertension. Portal hypertension refers to increased pressure within the portal venous system. Basically what happens is there are massive structural changes associated with fibrosis. And those cause increased hepatic vascular resistance creating hypertension in the portal venous system. When the portal venous system is tense like that, it causes a backflow of blood and accumulation of blood at sites of anastomosis between the portal and the systemic blood. And so there's a few areas where there's typical anastomosis between the portal and systemic blood. And you attend to get varicies there. Do you guys remember from anatomy where these happen? So I think first aid sums it up very eloquently. The anastomosis happen in the gut, the butt, and the kaput. So let me break that down. The gut refers to esophageal varicies between the left gastric vein of the portal system and the azygous veins of the systemic venous system. So you get esophageal varicies in the gut. And then the butt refers to rectal varicies. Do you remember which vessels are involved in rectal varicies? So in rectal varicies it's the superior rectal veins of the portal system and the middle and inferior veins of the systemic system. And then finally the kaput. So this is actually found around the umbilicus. So you get varicies between the para umbilical vessels of the portal circulation and the small epigastric veins of the systemic circulation. So this leads to distension of vessels around the umbilicus and it leads to like the snake-like pattern around the umbilicus which is called kaput medusa appearance, like the head of medusa. And so that's why you know that the umbilicus is referred to as kaput. So gut but kaput. If you don't remember the exact vessels don't worry as long as you kind of know esophageal rectal umbilicus, that should be good enough. Now varicial bleeding is a life-threatening complication in patients with cirrhosis and patients with cirrhosis are also going to have a higher tendency to bleed. Why would that be? Remember we talked about liver failure and failure to produce coagulation factors. So the liver makes all these coagulation factors but if it's synthetic function is poor um you're going to get low coagulation factors and you're going to be at a higher risk of bleeding. So how do we manage esophageal varicies? So you'll learn once you get to the wards there's a whole protocol for anybody with a GI bleed, you know you have to make sure they have two large bore IVs. You have to make sure that you're giving them IV fluid um to support their blood pressure but you also need to type and cross them and give them blood as soon as possible. Um and then you know ultimately what you're going to end up doing is consulting gastroenterology because what they really need to do is do an upper endoscopy. Um and physically go in there and usually band the varicies that are bleeding so that they can physically stop the bleeding. But there's also some medical management that we use in conjunction with esophageal banding. Do you guys know any medications that could be helpful in immediate management of varicial bleeding? So anytime patients have upper GI bleeding it's important to initiate a proton pump inhibitor for GI prophylaxis to prevent against stress ulcers from lack of blood flow to the stomach. And then another helpful medication is octetriotide also called somato statin. So octetriotide is a drug which basically is like somato statin and that can cause planknic vasoconstriction and kind of help decrease the blood flow to the esophageal varicies that are actively bleeding. And then let's say a patient does develop varicial bleeding. And you know they come to the emergency room, they go through the whole thing, they get those medications, GI takes them for the endoscopy and does banding. When you send them out of the hospital, is there any medicine you want them to be on long term? So it's good to start them on a beta blocker such as either perpranolol or natalol to help dilate those vessels and reduce pressure in them to prevent them from rebleating. Okay so important to remember that immediately you want to do like a proton pump inhibitor as well as octetriotide and then in the long term you want a beta blocker to prevent them from rebleating. Now my last question for you regarding esophageal varicies of course, what if the same patient who has esophageal varicies also has a cytis? Because remember that was the case for a 56 year old man, he also did have some esitis. What do we do for him? So with esitis as well as you know in the setting of varicial bleeding, there's thought to be a risk of translocation of the gut bacteria whenever they bleed. And so generally if a patient does have esitis and they start bleeding from esophageal varicies, you do want to start them on an antibiotic for prophylaxis for a condition called SBP or spontaneous bacterial paratonitis. And I think this is a great segue into our next complication of cirrhosis, spoiler alert. Let's say our patient appeared infected, he was febrile, labs showed leukosytosis, meeting sepsis criteria, florid sepsis criteria, also had a cytis. What should you be worried about? The belly is very, very tender on exam. I just gave you the answer but if you got it, pat on the back. It's spontaneous bacterial paratonitis, also known as SBP. What is SBP? So this condition refers to infection of the acidic fluid. And it's called spontaneous because there's no definitive source. It's thought to be most likely from just spontaneous translocation of the gut bacteria. And again in the setting of a GI bleed, you're more likely to have that spontaneous translocation. So that's why we start them on prophylaxis. Now I think this question is a little beyond the scope of step one. But how would you diagnose and treat spontaneous bacterial paratonitis? Remember I said earlier that paracentesis is a very useful tool, not just as a therapeutic tool but also as a diagnostic tool. If you are suspecting that patients have SBP, you can get a paracentesis and studies will typically show a white cell count. as well as a certain percentage of neutrophils. What you have to do then is calculate the number of neutrophils based on the percent that you get and the total white blood cell count. If that number that you calculate is greater than 250 neutrophils, that is pretty much diagnostic of spontaneous bacterial paratinitis. And typically you would then initiate a third-generation cephalosporin such as septrioxone for the treatment of S.B.P. Great job, guys. I know we just kind of briefly touched on some of the major complications of cirrhosis. There are some more complex things that can happen as well, which I think are well beyond the scope of step one. One such example is a condition called hepato renal syndrome, which is when you get renal injury in the setting of splanknick vasodilation and renal vessel vasoconstriction. But unfortunately, by the time patients get to hepato renal syndrome, their prognosis is very, very poor. Unfortunately, the process of cirrhosis, as I said, is not reversible. It's kind of like permanent scarring of the liver. So a lot of treatment just revolves around managing complications, preventing progression and preventing the adverse outcomes. And then, of course, you can treat the underlying condition. You can seize insults such as alcohol. If they do have an autoimmune condition, you can definitely start agents to prevent inflammation. But again, it's really difficult to prevent-- it's really difficult to reverse cirrhosis. In fact, it's impossible. What you can only do is manage the complications and prevent it from worsening. Now, once you get to the clinics, you'll learn this. But there are certain scores, such as the meld score and child's pew criteria, that help define the degree of cirrhosis. And basically, they look at different findings. I think child's pew looks at, like, if they have hepatic encephalopathy and things like that. The meld score looks at their labs, including their transaminase levels or sodium levels. And based on, you know, how severe things are looking, they can help kind of define the degree of cirrhosis and they can help prognostically. There is a procedure, also, that you should kind of be familiar with. It's called the tips procedure, trans jugular intra hepatic portosystemic shunt. That's a big word, but essentially, what they do is they try-- it's a procedure meant to help alleviate portal hypertension, which is a major complication of cirrhosis. And I have seen this done sometimes with palliative intent in patients who just have so much recurrent ascites from a lot of portal hypertension. When cirrhosis is really, really end stage, the only true cure for it is liver transplant. And this is, again, for patients who meet criteria. There's very complex criteria involved in liver transplant medicine. A lot of patients won't qualify. I rotated on the transplant service when I was in medical school. And it's very interesting, you know, patients who have alcoholic cirrhosis, they have to demonstrate that they have stopped drinking alcohol for a certain period of time. And that they have the social support in place to be able to remain abstinent from alcohol. And again, this is why I say that cirrhosis is so interesting. You have a lot of very specialized doctors managing these patients, because not only do you need hepatologists, but you also need transplant liver surgeons, and so on. So it's a very multidisciplinary, very interesting disease process. So I'm sorry to kind of go on this kind of, you know, distract you guys with a rant and kind of talk about all these different complications and all these clinical applications of cirrhosis. I think I'm just kind of babbling here, because I think it's so interesting. But again, the major takeaways that I want you to have, especially at the level of step one, is just that cirrhosis is a complicated topic, and it shows up a lot on the exam and in the words. And it's super cool because the complications are so systemic, because liver is so integrated with the whole body. So I just want you guys to quickly review right now the pathophysiology and understand why we see what we see. What finding do we get because of the build up of indirect bilirubin? Johnness, remember the indirect bilirubin accumulates, makes you look yellow. How about the decreased estrogen? What did we say that causes? So those skin findings of pulmonary erythema, spider angiomas, as well as gynecomastia, antisticular atrophy, you can see amenorrhea in females. How about the low albumin? What happens? Ascites. Remember we said that albumin helps maintain oncotic pressure in the vessels, and without it, the vessels will just third space fluid into the interstitial space, leading to ascites. How about the build up of ammonia? What does that lead to? Hepatic encephalopathy. And remember the key exam finding for hepatic encephalopathy? Asterixis. And then what about portal hypertension? What are some complications of portal hypertension? So as we kind of said, in addition to low albumin, portal hypertension contributes to ascites. But then further complications can include esophageal bleeding through the varices as well as SBP. So great job, guys. Thank you so much for listening to this episode. And again, thank you so much for the great support that we've had for the podcast in the last couple of weeks. It's been really great to get this great feedback from you. And I hope you guys continue to enjoy these episodes and continue to like, follow, subscribe, great review, whatever it is. If you found this episode helpful, most importantly, I really, really do encourage you to subscribe to the podcast so that you'll get notified whenever we release episodes. And we do try to release episodes every single Sunday. If you have any questions, comments, concerns, you can always visit our website at spoonfulofsugar.org and you can post them under the link for this episode. And I'm always reaching out if you are a third or fourth your medical student and you're interested in reaching out to us and recording an episode to join our team. Please email us at [email protected] and we would love to have you on board. There's a lot of upcoming med students that I'm excited to work with in the future. And I just wish you guys the best of luck with studying. Hopefully this podcast helps you get outdoors a little bit and not feel bad about leaving your books behind. Or I hope you just get outdoors a little bit without any kind of study material playing in your ears. It's really important to kind of balance the stress of studying with just enjoying life. So I think that's enough for me. And I just want to say good luck to you guys. If you ever have an SOS moment while studying, remember that spoonfulofsugar is always here to help the medicine go down. (upbeat music)