welcome back to mad medicine in this lecture we're gonna be discussing g6pd deficiency if you guys don't know on our youtube channel youtube.com forward slash mad medicine you can find our playlist for step one hematology and don't forget to like come and subscribe we post brand new videos every single day for you guys so with that being said let's begin by talking about normocytic anemias normocytic anemias are anemias that are classified by an MCB that is normal 80 to 100 and they can be subdivided based off of norma snort nan hemolytic excuse me nan hemolytic anemias and hemolytic anemias and the hemolysis can be subdivided based off of intrinsic causes and extrinsic causes so let's talk about some intrinsic or sorry i talked about some hemolytic anemia specifically when it comes to the intrinsic causes you have issues that are occurring within the red blood cell and these can be due to membrane defects issues with the membrane you can have enzyme deficiencies occurring and you can have hemoglobinopathies issues with hemoglobin itself that can lead to an intrinsic hemolysis and then you have extrinsic causes of hemolysis problems that occur outside of the cell and these can include autoimmune issues you can have issues with blood vessels so microangiopathic and macro angio Pathak disorders and you can have infections that can also lead to hemolysis especially extrinsic hemolysis now one thing to understand is because your body is lysine red blood cells your bone marrow is gonna produce more red blood cells and in the production of more red blood cells some immature red blood cells will be released and you will see an increase in reticulocyte count mainly greater than 2% normal is going to be one to two percent and in hemolytic anemia you'll see 2% a non hemolytic you will see normal reticular reticulocyte counts now let's talk about g6pd deficiency we said earlier that this disorder is mainly due to issues in the membrane so this is gonna be an x-linked recessive enzyme deficiency disorder that leads to intra and extravascular hemolysis because it's gonna render the red blood cell more susceptible to oxidative stress we're gonna talk about that a second but just understand this is x-linked recessive very very important because you could be asked about the probability of someone getting this disorder from their parents now talk about the pathogenesis and how this ends up happening where patients red blood cells are more susceptible to oxidative stress normally our red blood cells are in a very high-stress environment that is so true think about what's in your blood there is there's there's carbon monoxide there's oxygen there's even hydrogen peroxide and that is the main culprit h2o2 that is the main issue that we are facing nowadays in our bloodstream okay the main issue this main issue were campaigning against in this in this in this disease so you're hydrogen peroxide that can lead to a lot of oxidative distress on our red blood cells but luckily we have created a mechanism of preventing the oxidative stress and it's due a molecule called NADPH NADPH is produced by the HMP shunt and it's produced via the help of g6pd okay that's very important the enzyme that is missing at the moment now what ends up happening is because you have produced NADPH NADPH is going to produce a molecule or called glutathione this is an antioxidant so NADPH is going to reduce glutathione into its active form and when it reduces glutathione its glutathione is going to be able to neutralize hydrogen peroxide that's what's happening it's gonna activate essentially NADPH is going to activate glutathione which is then gonna attack hydrogen peroxide and it is going to negate the effects of hydrogen peroxide now if you don't have functioning g6pd you're not gonna be able to produce nadph and that means you're not going to be able to reduce glutathione so you're gonna have a decrease in reduced glutathione and that's gonna lead to increased activity of hydrogen peroxide and more red blood cell damage very very important now the important thing to understand is all of this is happening because of a reason it's not like our body automatically starts with lice in white blood cells not like our body automatically starts producing hydrogen peroxide in them that are going to cause this these problems in patients who have g6 deficiency g6pd deficiency oxidative stress is usually going to be caused by infections drugs like primal colon dapsone and sulfur drugs are very very important as well as favo beans or fava beans fava beans are a type of bean which end up leading to increased oxidative stress especially in patients who have g6pd deficiency now in this case you need to know father beans for step 1 because it is one of those fun facts that the examiners can ask you just to test if you understand the pathogenesis behind g6pd deficiency so very important do not forget fava beans it's only only associated with g6pd otherwise you can forget it for every other other disease now hemolytic anemia is gonna present after this oxidative stress again you have to be exposed to some some sort of stress that's gonna cause oxidation for this to occur usually one of these three things can will be will be the main cause of g6pd deficiency oxidative stress now when it comes through your clinical presentation you're gonna see a patient who's gonna complain of hemoglobinuria and back pain and this is gonna be after they become exposed to something that will lead to an increase in oxidative stress now hemoglobinuria makes sense your red blood cells are being lysed and the hemoglobin is gonna go through your kidneys into your urine and it's gonna be excreted through the urine now because hemoglobin is going to the kidney you're gonna have back pain due to the nephrotoxic effects of hemoglobin and you can also see jaundice dark urine and anemia so just keep that in mind now while we are talking about g6pd you should also be aware that there are two main variants two main variants one is a mild form and one is a more aggressive form so in the African variant you're gonna have a mildly reduced a half-life of g6pd which means that you are still going to be producing NADPH but not as much but that means you're gonna have a mild intravascular hemolysis what's oxidative stress this is going to be the mild form of g6pd deficiency now the other form the Mediterranean variant is going to be the extreme or it's just like severe form of g6pd deficiency in this case we have a very marked reduction in the half-life of g6pd and that's gonna lead to an increase in intravascular hemolysis with oxidative stress you don't have as much g6pd as you should as you normally would but every a reduce a significantly a significant reduction excuse me of g6pd and that's gonna lead to more severe symptoms when patients are exposed to oxidative stress now this is all believed to play a role in protection against Plasmodium falciparum plasmodium falciparum aka malaria infects the red blood cells and because you don't really have in good red blood cells that can prevent that can protect themselves from oxidative stress you're really not gonna be able to have a infection of malaria the malaria isn't gonna be able to stay comfortable in the red blood cell because the red blood cell is pretty much being lysed when it's in an oxidative stress environment and clearly an infection can also lead to oxidative stress like we said earlier so malaria is gonna lead to its own destruction in this case now when it comes to diagnosis and treatment you can use a Heinz preparation to screen for the disease the Heinz preparation is gonna look at precipitated hemoglobin that can only be seen because of the stain the reason why is because dekma sites and Heinz bodies are seen on blood smear and the Heinz preparation is used to look for Heinz bodies so let's talk about Digman sites first dekma sites are bite cells right here like you see this little bite has been taken out of this red blood cell this is a dekma site now they are associated mainly with g6pd deficiency that's very high-yield you're only gonna see that message mainly in g6pd and deficiency and they're associated with Heinz bodies at Heinz bodies are oxidation oxidative hemoglobin mainly the sulfhydryl groups have been oxidative I have been oxidated to disulfide bonds and this is gonna result in precipitation of hemoglobin now splanchnic the splenic macrophages are gonna remove this precipitating hemoglobin and it's gonna resolve in the bite cell that is very and this is what a Heinz body looks like as you can see in these red blood cells you have this little tiny area right here right here right here of precipitating hemoglobin this is done by looking through a Heinz preparation and keep in mind the Heinz body is just the soulful hydro groups of hemoglobin being oxidized to disulfide bonds and then then the precipitating now when the splenic macrophages take a bite out of the cell they're gonna remove this area okay they're gonna remove the area where the hemoglobin has precipitated and when they remove that area you're gonna just get a bite cell and that is how dekma sites are formed exactly how they're formed so this is gonna be associated with g6pd as well boom and it's gonna be associated with dekma sites because the splenic the splenic macrophages are gonna remove this area and you're gonna be left with a bite cell boom pretty high yield now enzyme studies can also be done to confirm the deficiency and it's usually done weeks after the resolution of the hemolytic episode once a physician suspects g6pd deficiency now the treatment is very simple for this case like we said these patients aren't just having hemolysis occurring out of nowhere it actually happens due to patients being exposed to an oxidative stress so the main thing you can do to treat these patients are make sure they prevail avoid the trigger so if they're eating fava beans if they're on like a Mediterranean diet they should probably stop they should definitely stop eating fava beans and if they're on a drug that's inducing it you want to try to avoid that drug and if they have an infection you want to treat the infection to make sure this patient gets better and to make sure that the red blood cells are not licensed g6pd deficiency in a nutshell mainly you have issues with g6pd and because you have issues with g6pd you cannot reduce glutathione and you're gonna have more oxidative stress from hydrogen peroxide leading to hemolysis you want to watch out for infections drugs like primaquine dapsone and sulfur drugs and fava beans and when it comes to treatment you want to look at avoiding those those triggers and when you're diagnosing these patients and you look under the microscope you're gonna see Heinz bodies with the Heinz prep and you can see Doug my sights and the Doug my sights are happening because the splenic macrophages are removing the hemoglobin precipitated Heinz body and that is pretty much all you need to know for g6pd deficiency thank you so much for watching don't forget to Like comment and subscribe to our channel new videos every day every single day you can follow us on instagram at Mad medicine and on Twitter at its mad medicine and you can listen to these lectures on your favorite podcast service for free just search mad medicine and we'll pop up