Cram The Pance - S1E10 Metabolic Disorders

Episode Date: January 29, 2021

G6PD Deficiency, Pagets Disease, Phenylketonuria, Rickets review for your Pance, Panre, and Eor’s.►Paypal Donation Link: https://bit.ly/3dxmTql (Thank you!)--- Support this podcast: https://anchor.fm/scott--shapiro/supportBecome a supporter of this podcast: https://www.spreaker.com/podcast/cram-the-pance--5520744/support.

All right. So today's podcast is going to focus on metabolic disorders. And this is from the GI section of the pants. So what this involves is going to be G6PD, Padgetts, phenoketoneuria, and Ricketts. We're going to go over those four topics today. And again, this is the metabolic disorder section of the GI Pants blueprint from the NCCPA blueprint. So let's start with G6PD. So what G6PD is is a genetic disorder that causes breakdown of red blood cells in response to an oxidative stress. And this leads. And this leads to a G6PD is, is a genetic disorder that causes a genetic disorder that causes breakdown of red blood cells in response. And this leads. And this leads. And this leads. And this to episodic hemolytic anemia. So that's the main thing you need to know for G6PD. They're going to have these episodes of hemolytic anemia. So what are some of the risks? Well, this is an X-linked recessive disorder, so it's obviously going to be most common in males. African-Americans are going to be at a higher predisposition for this.

And other regions where malaria is common. So Africa, Asia, Middle East. And the reason is because the same individuals in these areas who develop the mutation in red blood cells to protect against malaria, which is prevalent in these areas, also have a deficiency in the red blood cells that can lead to breakdown of the red blood cells from oxidative stress. So these individuals in these regions that are prone to malaria and have built the mutation to protect against it, also have this deficiency that can cause breakdown from oxidative stress. So as far as the pathos,

G6PD is an enzyme that protects red blood cells from damage. So this is G6PD deficiency. So what G6PD does is it turns something called NADP to NADPH. And NADPH is a molecule that generates free radicals in immune cells and protects the red blood cells from oxidative stress. So if you have deficiency in G6PD, you're not producing enough of this NADPH. So you don't, you don't, you don't, you don't, don't have this protection of the red blood cells against oxidative stress. Now, if a patient's exposed to periods of oxidative stress, whatever the cause is, which we'll go over that in a minute, this is going to result in denatured hemoglobin, which are known as Heinz bodies. And remember that because that's very important. That's one of those key terms you need to know. Heinz bodies is this denatured hemoglobin from the breakdown of the red blood cell. All right. Now, as far as the causes, there's really just three causes that you need to know. That's infection, fava beans, which is interestingly, another one. I'll go over that. And then medications. These can all lead to oxidative

stress, which is going to break down those red blood cells and these individuals that are prone to this. So infection is going to be your most common cause. Infection is an inflammatory response where oxidants such as nutrifils and hydrogen peroxide are produced. And this oxidation challenges the red blood cells and it just causes stress, which can cause them to break down and denature and turn into those Heinz bodies. So that's going to be your most common cause. Medications is going to be another one. Certain medications like dapsone, sulfa medications and higher quantities. Primaquin and nitrofurantoin is another one too. Those are some of the medications that you should know. These can all lead to oxidative stress. And the most interesting is fava beans, also known as broad beans. So these beans contain proteins called vizine and covesine. These are two different proteins that are found in fava beans. And what they do in a favel bean is it prevents them from rotting and just going bad. But the same proteins that protect it against this can also cause rapid oxidation in the body. And again, this is going to lead to oxidative stress.

So those are the three things you need to know, infection, medications, and fava beans. How is this patient going to present? Well, most of the time, unless they're going through an episode of this oxidative stress and they're, they have hemalytic anemia, they're going to be asymptomatic. They're going to feel fine. but when they do when they are exposed to oxidative stress they're going to have symptoms anybody else would have with hemolytic anemia so what are some of those symptoms well jaundice is going to be a big one and that's from hemolytic anemia uh the reds brettes i'm sorry the red blood cell is broken down billy Rubin which is a byproduct of red blood cell breakdown accumulates in the jaundice so that's why you get jaundice and hemolytic anemia they're going to have dark urine again this is from the intravascular hemolysis coming out in the urine splenomagely again the spleen is is working hard to break down and clear out all of these red blood cells. And then they also may have back in abdominal pain. And this is basically from the red blood cells being filtered out by the kidneys.

It can cause an acute kidney injury. So you may have some abdominal flank or back pain from the kidneys kind of being stressed. So those are all some of the symptoms these patients may have. As far as diagnosis, you're going to do a peripheral smear. And on the peripheral smear, you're going to see two things. So again, like we talked about before, you're going to see Heinz bodies. So again, Heinz bodies are these clumps of denatured hemoglobin attached to the red blood cell membrane, left over from the oxidative injury that the

red blood cell endured. So you have these little Heinz bodies attached to the erythorocyte cell membrane. So that's Heinz bodies. And then you have something called bite cells, which is also a form of schistocytes. So these are literally red blood cells that have a bite taken out of them. and what happens with this is red blood cells that have these denatured hemoglobin the hind's bodies when they enter the spleen the spleen removes the denatured hemoglobin and literally takes a bite out of the red blood cell and you have these bite cells so it's exactly what it says is there's like a bite taken out of the red blood cell and it's the spleen clearing out that denatured hemoglobe and taking that piece out of the red blood cell the way i always remember this was hind's bodies like hinds ketchup

makes the cells more tasty. So you have Heinz bodies on them and the spleen wants to take a bite because they has a tasty ketchup, Heinz ketchup on them. So super easy way to remember that. And then what your labs are going to look like. So that's what your peripheral smear will look like. Your labs are going to be reflective of hemolytic anemia. So you're going to see increased.

So if you remember this, your hemolytic anemia labs are going to be increased reticulocytes, increased indirect bilirubin and decreased haptoglobin. So let me go over why you see those. So reticulocytes are basically baby red blood cells. They're immature red blood cells. And this is because all of these red blood cells are being broken down and dying out. So this is rapidly producing more red blood cells. So you have an increase of all of these little baby immature red blood cells.

That's your reticulocytes. So that's why you see increased numbers of those. This is cranking them out as fast as they're dying off, this better and replace them. So you have all these new immature red blood cells. You also have an increase in indirect billy rubin. This is just simply from the breakdown of red blood cells. cells that you see the increase in indirect billyrobin. And then you have decreased haptoglobin. So the job of haptoglobin is to clear free hemoglobin from destroyed red blood cells. So it's produced in the

liver. And during hemalytic anemia, it's overworked. The liver can't produce enough of this haptoglobin to keep up with the demand to clear out all of these destroyed red blood cells it's seeing. So it's just going to be found in decreased levels. So that's why you see increased reticulocytes, increased intertriculocytes, increased indirect bilirubin and decreased haptoglobin. So that's the way, that's what you're going to diagnose these patients. And now how are you going to treat them? Well, normally it's self-limited. You know, so most of the time they don't need anything.

But if it's really severe, they have a really bad, a severe renal injury. You can use dialysis. And if there's an underlying infection, of course, you want to treat the infection. If it was from food or med, stop the med, stop the food. Most of the time, it's just going to be discontinue the offending agent. If it was from a food they ate, if it was from a medication, just discontinue it. that's the majority of the time what you're going to do, treat the infection if that's the cause of oxidative stress. And then you can also, an important thing to note is that this increased

rate of red blood cell production can lead to folic acid depletion. So normally you want to give these patients supplement them with folic acid to help them replenish their folic acid that may be deficient in these patients. Now, there's a bunch of stuff I went over for G6PD. The way I remember some of the key points that you need to know for G6PD is I told you before G6PD causes these episodes of hemolytic anemia. So I take the word anemia and break it down and this is what I got for you. So anemia, African American, remember, that's the most common race you'll see this in. The second one, N in anemia, nitroferentoyan. Remember, that's one of the medications that can cause the oxidative stress. E stands for episodic hemolytic anemia. That's what this calls.

causes. M stands for males. Remember, this is an X-linked recessive. So males for M. Another M is medication. So males and medications. I in anemia stands for infection. Remember, that's your most common cause. And then A is going to be your most common treatment, which is going to be avoid offending agents. So A, African American, N, Nitro-Furantoyan, E, episodic chemolytic anemia, M males, most common, and M medications, I infection, and A, avoid offending agent. P-D, kind of a little bit involved, but, you know, there's really just some key points that you need to know. So if you focus on those things and kind of just the mnemonic I gave you, those are the main things that you need to know for that. So moving on to Paget's disease.

So I just want to give you a quick refresher before you get into Paget's disease. A couple of things you need to be familiar with before we go into this. So osteoclast and osteoblasts. I want to refresh on what those things are if you don't remember or if you haven't gone over it yet. So osteoclast activity is what breaks down bone. It can replenish calcium levels in your body by breaking down bone, but osteoclasts are going to be breaking down a consuming bone. Osteoblast or osteoblastic activity is what rebuilds bone, synthesizes new bone formation. The way I remember that, osteoclast has a C, osteoblast has a C.

Osteoblast has a C. So osteoclast, the C stands for consume bone, because that's what it does, it consumes. And osteoblast has a B, and the B stands for build bone. So that's how I remember those two. So let's get into it. Padgetts is an abnormal osteoclastic and osteoblastic activity. So the body's breaking down bone really fast and is rebuilding bone really fast. What happens when you break down and rebuild bone really fast? You get abnormal bone remodeling. You get this kind of layered bone that's just big but not very strong. So you wind up with these long bones, skull deformities. The bones keep getting larger and bigger from all of the hyperactive breakdown and rebuilding. But, the bones that it builds are ultimately weak and fragile since these osteoblasts really can't keep up with the osteoclast activity. So the bones are really big and abnormally shaped, but they're not very strong. The bones in Padgett disease patients have this irregular mosaic pattern rather than

a tightly fit, like bound together structure that's found in normal bones. This is more like this this mosaic pattern. It's just very weak and these patients can obviously suffer some fractures because of this. So as far as the presentation, most patients about 70% are going to be asymptomatic. It could be in an incidental lab finding, which we'll go over later, that you find this, or an unrelated imaging study. But most of the time, they're going to be asymptomatic, surprisingly. When patients do have symptoms, I'm sure you won't be surprised, they do have bone pain. That's one of the most common things. And this is normally due to, they can have these little micro fractures of the irregularly formed bones. Another thing that can cause some of the bone pain

that they have is spinal stenosis, which is pretty common in Padgetis disease. Then obviously another big thing is they're going to have bony deformity. So they may have bowing. They may have frontal bossing, which is a growth or protuberance of the forehead of the skull. And the most common areas for this to be involved in is going to be the femur and the pelvis in about 75% of patients and the skull in about 37%. So that's the most common areas to find Padgetts. And another interesting thing that these patients can have is actually hearing loss. And one of the possible reasons for this is due to decreased bone mineral density of the capsule of the cochlea. Remember, it affects all bones, and the cochlea is a bone.

And it can also be caused by compression of surrounding bones of cranial nerve 8. Remember, which controls your hearing. These patients may also have facial pain, loosening of teeth when the facial bones are involved. So a lot of different things, but generally asymptomatic. If they do have symptoms, they may have hearing loss and bone pain from the micro fractures and things like that. So how do you diagnose Paget's? So one of the biggest things, the main thing that you need to know is that they're going to have an increased alkaline phosphatase. If you don't remember anything else, remember that about Paget's. That's the most important thing. And I'll tell you how I remember that in a minute. So in Paget's increased alkaline phosphatease. Their calcium is going to be normal. Their Ptch is going to be normal.

Phosphate's normal. It's only the alkaline phosphatase that's normally elevated. And this is due to the increased osteoblastic activity. Alkaline phosphatase is attached to osteoblasts and are released during increased osteoblastic activity. So that's why you see increased alkaline phosphate taste. Remember that. On x-ray, you may see increased trabecular markings due to the increased sclerotic phase during the sclerotic phase. And then you may see something described as a cotton wool appearance of the skull on x-ray, and that's due to these thickened and sclerotic patches of bone that you can see in the skull. So cotton wool appearance on x-ray, something else that you'll see. As far as treatment, if they're asymptomatic, you're just going to observe. There's really not much else to do. And if they, you know, if they start having problems, bisphosphonates.

So londrinate and that class of medications. So really kind of easy to remember for treatment. Most of the time, you're not going to do anything. If you do give them something, it's going to be bisphosphonate. So remember that pretty straightforward. And then the way that I remember Pagets is that you remember, the way that I remember that it's increased alkaline phosphatase is that I take the letters from Paget, P-A-G-E-T, and I switch around alkaline phosphatase, and I say, Phosphatease alkaline greatly elevated today. So maybe not the best mnemonic, but I never forgot it.

So I just say Paget's, the letters P-A-G-T from Paget, and I say, phosphatease alkaline, obviously reversed, greatly elevated today. So that's how I remember that it's increased alkaline phosphatase. That's really the only thing you need to know for the labs. And again, treatment's pretty straightforward. It's just going to be bisphosphonates. All right. Let's move on to something a little bit more involved. And that's phenoketoneuria. So this is an autosomal recessive disorder that results in decreased metabolism of something called phenylalanine. Probably going to mess up saying that at some point, but phenylalanine. So autosomal recessive disorder that results in decreased metabolism of phenylalanine.

And it leads to an accumulation of phenylalanine in both the bone and the urine. So that's what this is. And why does that matter? So first of all, let's go over where phenol alonine is found. So phenol alonin is actually found in a lot of proteins. So eggs, chicken, pork, fish, beans, milk, a lot of proteins you'll find this. Another interesting place you'll find it is actually in aspartame in some diet sodas. And I don't know if you've ever seen the side of a, I know I've seen it before on the side

of a Diet Coke. It says this contains phenylalanine, warning. I always wondered why that was so important. But this is actually why, because this can be pretty scary for these patients that have this phenokyotone urea. So moving on, what is the actual patho behind this? So phenylalanine can be toxic to the body and increase level. So what the liver does is when you consume phenylalanine, the liver creates an enzyme called

phenylalanine hydroxylase that converts phenolin, which can be toxic to the body, into something useful called tyrosine. So this is a useful amino acid that's a building block for proteins. It's essential for neurotransmitter production. It helps to build epinephrine, nor epipid dopamine. And in patients with phenocutonuria, their liver isn't producing phenolamine hydroxylase. So instead of breaking this down into something useful tyrosine, you're going to get a buildup of the phenylalanine, and you're going to be deficient in tyrosine. So that's basically all this is.

The phenol alenine can't be broken down, and it's building up and it's not turning into tyrosine, which is what the body needs. So how do these patients present? There's a few different ways they may present. One thing is that they may have intellectual disability, and this is due to the toxic levels of the phenylalanine in the body. that can affect brain development, et cetera, these patients. Another thing is microcephaly. So the fetal brain growth is negatively infected, again, by the increased levels of the phenylalanine and the maternal circulation.

So those are both due to the toxic levels of the phenylalanine. And then there's a couple other things that are affected due to the decreased tyrosine, which I'll go over in a minute. So the urine also, another important thing is that these patients may have a must or mousy odor to both their urine and their sweat. And that's because of this exosphenolalanine being flushed out through the urine. And it's kind of broken down to this something called phenylacetic acid, which is a byproduct of phenylalanine degradation. And that's why these patients, remember that because this is definitely going to come up in the vignette. If you do have

a question, they're going to have this musty or mousy odor to their urine and their sweat. They may also have seizures due to the toxic levels of this. And then there's something else that's interesting. And this is related not to the amount of phenolololony, but due to the decrease in tyrosine. So these patients with phenoketone urea will normally have light pigmentation of both their eyes and their hair. So they're normally going to be blonde hair, blue eyes, and why does this happen? Well, they have decreased melanin production. And since melanin is predominantly synthesized from tyrosine, and these patients have a deficiency in tyrosine, these patients don't produce enough melanin. So they're going to have light hair, light eyes, typically blonde hair, blue eyes.

So that's another thing that you should know, because that may be in the vignette. That would certainly be an important thing to be in the vignette. So how do we diagnose them? Well, all newborns, at least here in the United States, are typically screened for phenoketone urea. They normally do this through something called a heel prick test, and they test for some other things as well as cystic fibrosis, congenital hypothyroidism, but they always test for PQU because they want to treat it early if it's discovered. So normally they do, all newborns get screened for this in the heel prick test. And then another way you can test for it as well is quantitative serum phenylalanine. That's another way too. But normally if patients do have this, it's discovered shortly after birth, normally within the first

24 to 48 hours on laps. So how do you treat these patients? Well, remember, there's two things that's wrong with these patients. They're low in tyrosine and they're high in. phenylalanine. So how do we decrease the amount of phenylalanine? Well, remember we talked about before, this is a dietary intake. So you're going to decrease the dietary intake of phenylalanine. So decrease cheese, eggs, fish, remember, aspartame and diet soda, decrease the dietary intake. And then how do we fix the other problem? They're low in tyrosine. Well, you just give them tyrosine supplementation. So it's pretty simple the treatment. Another thing as well is something called sapro-saproteran. And this is a medication that these patients can take that can actually

lower the phenolalinine levels, which allows them to have a less restricted diet in some patients. Because, I mean, a lot of people like to eat the foods that's high in phenolalanine and cheese, eggs, fish, you know, all these meats and proteins. And to not be able to eat these, well, this is a medication that can help them that they can take. So saproterin is a medication that can decrease the phenolalalene. So they can have some. in their diet. And that's more in like mild to moderate cases. And real severe, they have to avoid it. So let's move on to the last part. That's Ricketts. So Ricketts is a softening or weakening of bones in children. And it's most commonly due to vitamin D deficiency. So this is the child or the

pediatric version. Osteo malacia is when this happens in adults. So vitamin D deficiency in children. And this is a deficiency in the mineralization at the growth plates of long. bones and this can result in bony deformities growth retardation in these patients and vitamin d is responsible for absorbing calcium and phosphorus from the foods we eat and without vitamin d these patients don't have enough calcium to deposit and build bone and that's why you start to see all these problems that these patients have like the weakening and the softening of bones so as far as the etiology there's two different causes there's either calcium deficiency or it can be renal in origin So if it's caused from a calcium deficiency due to decrease vitamin D. Remember, vitamin D is what is able to, so you can get calcium absorbed.

This is called a calcipinic rickets, and that's from a calcium deficiency. And then if it's renal in origin, it's called a phosphopinic rickets, and it's due to renal phosphate wasting. So two different causes, one from calcium, one from phosphate. This is the two different etiologies. So how do these patients present? well remember this is a bony deformity so bone pain is going to be pretty common and it's most associated with something called pseudo fractures that can present in these patients so there's this band um of decreased bone formation or mineralization it can cause calluses at the at the end of these bones um and it can cause

calluses at the periosteum and things like that so they may have bone pain another thing that can happen is delayed fontanel closure so that's going to they're going to have these newborns or the These infants are going to have this soft spot that doesn't close, and it's caused by an incomplete closure of the anterior fontanelle. Some other things that they can have related to the bony deformities. They can have something called frontal bossing as well, and that's related again to the anterior fontanelle not closing. They can have bowing of the femur and tibia known as genuverum. And you'll probably go over this if you haven't yet, but there's something called genuverum and genuvergum. And the way you remember that is genuverum.

You think of rum makes you weak at the knees and your knees bow out and your legs bow out. And genuver gum, think of gum between the knees, making your knees stick together. And that's when you kind of have those knock knees or your knees stick together. But these patients have bowing of the femur and tibia. So it's known as genuverum. They also may have developmental delay of motor, of their motor milestones. Remember, because their bones aren't developing. so that's definitely something you may see as a developmental delay of the motor milestones.

As far as diagnosing, you're going to diagnose from labs and from x-ray. So your labs are going to show pretty consistent pattern of decreased calcium, again, because we're not producing vitamin D. So they're going to have decreased calcium, decreased phosphate. Remember, it depends on the cause. And then, of course, decrease vitamin D. So that's pretty consistent across the board. And then you're going to see an increased PTH, if this is from decreased. calcium, not the phosphatopinic cause that we went over, but increased PTAH, because remember,

PTAH responds to calcium. So if you have decreased calcium in the body, PTH is going to compensate trying to increase that. So increase calcium or increased PTH. And then you're going to see an increased alkaline phosphatase. And this is due to the high bone turnover and the increased osteoblastic activity. So you'll see increased alkaline phosphatase. So again, labs, decrease calcium, decreased phosphate, decrease vitamin D. You'll commonly see an increased PTH and then an increased alkaline phosphatase is what you'll see in these patients. Now, in X-ray, you're going to be looking at the long bones of these patients, typically looking at the wrist and the knees, because you want to look at the epiphyl plate of both

between the femur and the tibia and the radius and the ulna. And in these epiphacil plates of these long bones, you're going to see widening of the epiphousel plates. You may see a loss of definition of long bones. In particular, the cortex of long bones. can appear what they describe as fuzzy. So the cortex of long bones may appear fuzzy. You have this loss of definition. And then another one of these keywords that you need to know, Rachicchikrosary. I may or may not be saying that correctly, but Rachycti-Tic-Ticrosy. And this is at the costocondrial junction, so where the ribs meet the sternum, they're actually going to be enlarged. And if you look at the thorax of these patients, you'll see this line of it almost looks like beads across their thorax. And it looks

like, I don't know if you know the necklace I'm talking about, but the rosary, the rosary necklace with the beads on it, it kind of looks like that. And that's where they got the retictic rosary from, because at the costocondrial junction, they have these enlargements that looks like beads at that junction. So that's why they call it richictic rosary. So that's how you're going to diagnose. As far as treatment, it's pretty straightforward. They're deficient in vitamin D and calcium. So you're going to supplement vitamin D and calcium. That's pretty straightforward. In severe, symptomatic, hypalcemic patients. Remember, if they're severely hypalcemic, they may have seizures, cardiovascular instability. And these patients, they're going to require hospitalization,

IV calcium infusion, but that's just your severe patients. Otherwise, very straightforward, vitamin D and calcium. And guys, that's it for your metabolic disorders. I know there's a lot of material in a short amount of time, but hopefully that was helpful and hopefully those mnemonics do help you. And as always, good luck on your pants, your panorri, your EORs, and good luck in PA school. please leave me a review if you like this and let me know how you guys feel about the the podcast all right thank you