Transcription
Here we go, the third part of our lecture on sickle-cell disease. Today, we will discuss the clinical picture of sickle-cell disease. So grab some popcorn and enjoy the video, because it will be a long video.
In the previous video, when we discussed the pathophysiology of sickle-cell disease, we have said that in arteries, usually we have oxygen, so the hemoglobin S is soluble. Why? Because it's in the oxy form. But in the vein, there is low oxygen, so there is a problem. Why? Because hemoglobin S will precipitate and polymerize, because it's a deoxy hemoglobin S status. And when there is a deoxy status, it will polymerize, and the cell will sickle. By the way, any stressful event can trigger this, not just hypoxia, but also infection, trauma, illness, acidosis, of course, dehydration. This eventually leads to membrane changes, to lead to sickling of the red blood cells. We have two fates: one, extravascular hemolysis—where we mean the reticulo-endothelial system, most commonly splenic macrophages—will consume the red blood cells; this is hemolysis. Or, vaso-occlusion—these cells will clump and close this vessel, especially on the venous side of the capillaries. So this is the story of today's video. We have first, symptoms related to the extravascular hemolysis, and second, symptoms related to the vaso-occlusive crises.
First, symptoms related to extravascular hemolysis clinically have all signs and symptoms of anemia, which include pallor and tiredness. So we have fatigue, we have drowsiness, we have angina, we have murmur, we have exercise intolerance. We have a lot of symptoms, plus jaundice. Why? Because of the unconjugated bilirubin. Go back to my videos where I discussed hemolysis, extravascular and intravascular, and you will know that the unconjugated bilirubin is in excess due to the hemolysis. That's fine. So we will have urine discoloration, also known as Coca-Cola-like urine; splenomegaly, of course, the spleen's working hard to destroy all of these red blood cells; also these blood cells will clump and be trapped in the spleen; the spleen will swell; hepatomegaly, of course, because the liver is working hard to conjugate all of this unconjugated bilirubin; skeletal changes—yes, when the bone marrow cannot provide us with enough red blood cells because the hemolysis is consuming all of them, we need help from outside: extramedullary hematopoiesis. Medulla here refers to the bone marrow, extramedullary hematopoiesis. So we have some skeletal changes, such as chipmunk faces and a hair-on-end appearance.
Then, second symptoms related to the vaso-occlusive crises. So the red blood cell will get clumped here, okay, leading to ischemia and infarction, such as dactylitis, which occurs in kids; acute chest syndrome in adults; pulmonary hypertension as well; for the kidney, renal papillary necrosis; bone, osteomyelitis, commonly by Salmonella. Why? Wait, and you'll see. Bone pain; splenomegaly; splenectomy; splenic sequestration crisis; bone marrow aplastic crisis, especially by parvo B19. I've discussed this before in aplastic anemia, as well as the other video on pure red cell aplasia, so please go ahead and watch them. Recurrent leg ulcers, usually above the medial and the lateral malleoli. This is different from diabetes; diabetic foot ulcers are usually the heel and the sole of the foot, so this is different. Proliferative retinopathy and strokes in children. When we think stroke in general, I always imagine an old guy who is obese, has a lot of risk factors, such as going to McDonald's for 40 years straight, eating a lot of fat and junk food, having a big gut, going so this is usually the stroke, but here I'm talking about strokes in children. This is not usual, so please, when you see a stroke in a child, suspect sickle-cell disease, especially that they are African-American or from African descent.
So let's elaborate on some of these complications, and then we are done. Dactylitis means inflammation, so inflammation and painful swelling of the hand and foot. It's also known as hand-foot syndrome. Do not confuse this with hand-foot-and-mouth disease, by the way. What's the most common cause of hand-foot-and-mouth disease, which organism? Let me know in the comment section. Infarction of the metacarpal bones, also known as aseptic necrosis, which affects six-to-nine-month-olds. So dactylitis is a disease that affects kids; it's very rare for kids more than two years old. On the other hand, acute chest syndrome affects adults, not kids. So it's just me and you. The new segmental lung infiltrates—so if you do an x-ray, you'll see a segmental lung infiltrate, hopefully with some pleural effusion. Also, the mechanism may include micro-infarctions, of course you know why, because these sickled red blood cells accumulate in the small blood vessels, leading to infarctions; causes pneumonia; bone infarctions; and fat embolism. Sickle-cell disease affects the bone, which can lead to fat embolism; these emboli eventually go to the lung. Symptoms of acute chest syndrome: chest pain, which is a pleuritic pain; dyspnea; wheezing; cuff on arterial blood gas; you have hypoxemia. Another symptom is pulmonary hypertension, but this is not acute chest syndrome; this is another entity, but it's associated with sickle-cell disease. Atención, atención! Acute chest syndrome is a medical emergency, which will require blood transfusion. Acute chest syndrome is a medical emergency.
What's the effect of sickle-cell disease on the kidney? A lot of things, collectively called sickle-cell nephropathy. They may include, but are not limited to, pyelonephritis; chronic kidney disease, which can lead to diabetes insipidus; renal papillary necrosis. Why? Because the papillae are in the medulla; the medulla is very susceptible to ischemia; it's very hypertonic. So here is your cortex, and here is your medulla. This is very far away from the blood supply; it's very susceptible to ischemia. And in sickle-cell disease, already these nasty red blood cells are clumping and clogging the vessels, so ischemia will follow, and these papillae, these nice papillae, will necrosis and die and slough off in the urine and can lead to hematuria—can be microscopic, especially in sickle-cell trait, or gross hematuria, especially in sickle-cell anemia. Okay. Chronic interstitial nephritis can occur as well; inability to concentrate urine, why? Because the medulla is affected; the medulla is supposed to concentrate your urine. When there is ischemia to the medulla, your urine is not going to be concentrated; we call this isosthenuria. Okay, isosthenuria. Isosthenuria; stenos means strength; iso means the same. So we have urine which is the same power; concentration is increased power, more concentration; no concentration of urine is called isosthenuria. Eventually can lead to end-stage renal disease. Why is that? Because now people have escaped poverty; medical technology and healthcare have improved, so sickle-cell anemia patients are expected to live longer, so you can expect them to have end-stage renal disease down the road.
Mr. bone: avascular necrosis or aseptic necrosis of the femoral head or the head of the humerus; osteomyelitis. Why? -itis means inflammation. Osteomyelitis is an infection, and we will discuss that. They have something called autosplenectomy in sickle-cell disease patients. The spleen is screwed, so you are expected to have more infections, so osteomyelitis is now more probable. Which organism is the cause of osteomyelitis in sickle-cell patients? Salmonella. Why? Because you don't have a spleen. When you don't have a spleen, you cannot defend your body against the encapsulated organisms, and Salmonella is an encapsulated organism. Fat necrosis can occur as well. Now, the spleen—and that's a biggie—autosplenectomy or functional asplenia. But what does this even mean? You have these sickle cells; they occlude your blood vessels, leading to ischemia, then infarction; eventually they will render your spleen useless by 12 months of age. So now your spleen is useless, as if you have no spleen. Splenectomy means removal of the spleen, but you didn't have a surgeon removing your spleen. Who needs a surgeon? They are bad people. Autosplenectomy—I will remove my spleen metaphorically, because now I have explained but it doesn't have any function, as if I have removed it. Autosplenectomy. And when your spleen is useless, you're at increased risk of infection by encapsulated organisms, such as Strep pneumo, Haemophilus influenzae, Neisseria, and don't forget the Salmonella causing osteomyelitis, as we have discussed before. Problem number two: splenic sequestration. These red blood cells get trapped in the spleen; the spleen swells; painful enlargement of the spleen is called splenic sequestration. This is a medical emergency that may require blood transfusion. Hyposplenism means decreased function. Hyposplenism doesn't mean decrease of the size, but decrease in the function of the spleen; functional asplenia—without splenius plane? Why not just asplenia? Yeah, asplenia means you don't have a spleen. No, no, you have a spleen, but there is no function, so it's functionally absent; functional asplenia. Eeh. So problems of the spleen: autosplenectomy, you can call it functional asplenia, yeah, fine; after hyposplenism, it's fine. Problem number two: splenic sequestration crisis.
Now here's a collection: sickle-cell crises. There are a lot of crises happening in sickle-cell disease. Crisis usually means acute. So here's a problem: vaso-occlusive crisis—yes, it's a problem. Why? Pain; ischemia; infarction in many different organs, as we have discussed above, the first slide. Aplastic crisis; bone marrow aplastic does not synthesize; bone infarction will lead to pancytopenia. If parvo B19 affects the bone marrow, this will lead to pure red cell aplasia, and I have discussed the subject in a separate video, so please go ahead and watch it. Splenic sequestration crisis, okay. Hemolytic crisis, especially if G6PD coexists with sickle-cell disease. Dude, that's very bad luck. And now this is very high yield: any black person with unexplained hematuria, please go ahead and order a sickle-cell screen, doc. I have blood in my urine. Sure, sir, I will order a sickle-cell screen as soon as possible.
So in brief, sickle-cell disease symptoms are either related to hemolysis or related to vaso-occlusive crisis. The hemolysis is usually extravascular, due to an intrinsic red blood cell defect.
Now, quiz time. So my first question that I would like you to answer in the comment was: what's the most common causative organism of hand-foot-and-mouth disease? Then please answer these questions: most common in sickle-cell disease: one, what's the most common cause of death in children with sickle-cell disease? Blank. What's the most common cause of death in adults with sickle-cell disease? What's the most causative organism of meningitis in children with sickle-cell disease? What's the most common causative organism of bacteremia in children with sickle-cell disease? What's the most causative organism of osteomyelitis, and what's the second most common cause of organism of osteomyelitis in sickle-cell disease? What's the most common type of hemoglobin? Is it hemoglobin A, hemoglobin B, hemoglobin F, or other? Last question: what's the most common reason to seek medical attention in patients with sickle-cell disease? Please let me know in the comment section. I'll post the answer on my Facebook and Twitter accounts, so please go ahead and like me on Facebook and follow me on Twitter, and I'll see you in the next video, when we will discuss diagnosis and treatment of sickle-cell disease. Stay tuned.