Transcription
Sickle cell disease. I've talked about it before in four long videos but today's a quick recap if you don't have time to watch all my four videos. Sickle cell disease, very common in Sub Saharan Africa to protect the African population against the Plasmodium falciparum malaria. Evolution through the process of natural selection. The inheritance of sickle cell disease follows an autosomal recessive fashion.
Both mommy and daddy are carriers AS, and now twenty five percent of the offspring is normal. Fifty percent are carriers or sickle cell trait or hemoglobin AS, and the last twenty five percent is very unlucky abnormal sickle cell disease or hemoglobin s s so what's your point my point is a point mutation okay You know that your hemoglobin has two alpha chains and two beta chains normally. In sickle cell disease, there is a defect in the beta globin chain on HBB gene on chromosome number eleven. Non conservative missense point mutation. A single nucleotide polymorphism.
Single nucleotide has changed and now the amino acid yield is different. Instead of glutamic acid, now you have valine at position number six okay fine oxygen is anti sickling hypoxia is pro sickling that's why anything that will shift your oxygen dissociation curve to the right will cause sickling because shifting to the right means release of oxygen from the hemoglobin to the tissue and now your hemoglobin is having less oxygen and the vicious cycle goes like this no oxygen sickling membrane damage hemolysis so the mechanism or the path of physiology goes like this your deoxy hemoglobin which means hemoglobin without oxygen has a position which is a hydrophobic position Glutamic acid was hydrophilic. It didn't fit the position, but now you have valine which is hydrophobic. It fits the position Seamlessly, but there is a problem This will trigger the hemoglobin s to polymerize like this calcium influx then potassium efflux followed by water The cell is dehydrated. When the red blood cells dehydrated, it sickles.
It has two different destinations either to go to the spleen and get destroyed by the splenic macrophages or to go to the capillary bed and clog them causing painful crises. Okay. Is your hemoglobin a prone to sickling? The answer is yes. Hemoglobin f, the fetal hemoglobin is not prone to sickling.
That's why babies will never get sickle cell symptoms until six months of age postnatally. There is a nice drug called hydroxyurea. We can give to increase the amount of hemoglobin f and protect you against sickling. From Shakespeare, to sickle or not to sickle, this is the question. What are the causes of sickling?
One, hemoglobin has concentration more than 60. That's why sickle cell anemia has sickling while sickle cell trait, there is no sickling. Reason number two, increase the oxyhemoglobin concentration. Volume depletion when you have less volume, you have a relatively more hemoglobin. Acidosis, which shifts the curve to the right.
Hypoxemia because oxygen is anti sickling. No oxygen means sickling. You don't have any problem whatsoever in an artery because there is a sufficient amount of oxygen. However, in veins, there is less oxygen, hemoglobin s will polymerize, and now your cell will sickle. It has two different destinations either to get to the spleen to get destroyed by the macrophages This is extravascular anemia or to get to the capillary bed and clog it.
This is vaso occlusive crisis So the clinical picture will be subdivided into two sections. First, symptoms related to the extravascular hemolysis, and second, symptoms related to the vaso occlusive crisis. And we have discussed them before in our video on extravascular hemolysis and the comparison between extravascular and intravascular. Here, it's mostly extravascular. Second, symptoms related to vaso occlusive crises.
These sickled red blood cell will clog the capillary bed in different organs leading to different symptoms. First hand and foot dactylitis inflammation and painful swelling six to nine months of age dactylitis is extremely rare after two years of age on the other hand acute chest syndrome is an adult disease not children adults what is acute chest syndrome is a medical emergency what's that new segmental lung infiltrate and pleural effusion precipitated by pneumonia as well as bone infarction leading to fat embolism it's a medical emergency so please transfuse blood Sickle cell disease can also lead to pulmonary hypertension. What's next kidney sickle cell nephropathy a lot of diseases such as pyelonephritis interstitial nephritis, but most important, renal papillary necrosis. Why the papilla? Because they are in the medulla, and the medulla has a lot of hypoxia and hypertonicity, so sickling is severe there.
Next chronic abdominal pain what about the bone you can have a vascular necrosis or you can have osteomyelitis especially by salmonella why because your spleen is useless and salmonella is an encapsulated organism next spleen oto splenectomy not the surgeon that removed your spleen o two you have removed your own spleen by your sickle cells they clog the spleen causing ischemia and infarction and now your spleen is useless and you can get infected by encapsulated organisms such as strep pneumo haemophilus influenza neisseria as well as salmonella that's fine sequestration crisis this sickled red blood cell will get Trapped here the spleen will swell causing painful crises recurrent leg ulcers fine aplastic crisis. Welcome again parvo b nineteen proliferative reasonopathy strokes in children not in a 67 year old male with multiple risk factors stroke in kids, please suspect sickle cell disease Priapism is common in sickle cell disease, which is not fun. How to diagnose sickle cell disease? Prenatally by DNA. Getting the sample and do PCR or a leave specific hybridization.
How to obtain the sample? Through chorionic villus sampling or amniocentesis. Postnatally is different. CBC will show low hemoglobin and low hematocrit because it's anemia MCV is normal or slightly elevated reticulocytosis, of course, reticulocytes are increased except in a plastic crisis where reticulocytes will be decreased sickle cell screen add sodium meta bisulfide to the test tube and now oxygen tension will decrease and the cells will start to sickle and you can observe that peripheral smear or blood film you can have sickle cells target cells whole Jolie bodies all of these cells are present in sickle cell anemia but they are absent in sickle cell trait Gel electrophoresis is great. It will detect the hemoglobin s as well as the amount of hemoglobin s.
How to manage circle cell anemia? Daily folic acid. For a splenia or otosplenectomy you need to give both antibiotics and vaccinations antibiotics Penicillin v prophylaxis until five years vaccinate against pneumococcus meningococcus haemophilus influenza, which is a bacteria influenza virus hep b Vaso occlusive disease you rehydrate especially in priapism You give some analgesics transfusion antibiotics and your nice hydroxyurea to increase hemoglobin f Comparison between sickle cell anemia and sickle cell trait SSAS a s homozygous heterozygous the amount of hemoglobin here the hemoglobin s is 90% here it's 43% symptoms related to hemolysis as well as vaso occlusive crises here no symptoms except for a little hyposthenuria which is inability to concentrate urine as well as microscopic hematuria. On blood film, you will see sickle cells, target cells, whole jolly bodies. Here, you don't see any of these.
Treatment, folic acid, antibiotics, vaccinations and maybe transfusion no need to treat. It's very benign Please try to answer these questions. The answers are on Facebook or Twitter or you can comment below. See you