 To begin with, let's look at the main parts of each red blood cell, the membrane, the hemoglobin, the enzymes required to make energy, and aerobically in the case of red blood cells. If the synthesis of any of these three core components is disrupted, in particular ways, we're at risk of hemolytic anemia. If we have an inherited deficiency in certain RBC membrane proteins, our RBCs won't resemble the classic bioconcave disc. In hereditary spherocytosis, a complete lack of several proteins causes the RBCs to be produced as spherocytes, which are sphere shaped. They can't fit through the bottlenecks of the spleen, and are thus determined to be abnormal. They are then phagocytosed by spleen macrophages. Early treatment for this condition includes total splenectomy. Because the spleen is integral to our fight against bacterial infection, patients will then be required to take prophylactic oral antibiotics for the rest of their lives. In hereditary elliptocytosis, RBCs are prone to being deformed as they squeeze through your capillaries. Normal RBCs bounce back easily from this kind of stress, but again, a lack of membrane proteins makes these RBCs lose this ability. They are squished into a permanent ellipse and follow the same fate as spherocytes once they've reached the spleen. Let's look at issues with hemoglobin now. We're going just for the most common sickle cell disease. So normal hemoglobin schematically looks like this. Four separate globin constituents surrounding the heme molecule in the middle. With homozygous abnormal HBS genes, when your hemoglobin is in a state of deoxygenation, it tends to reduce polymers, long chains like this. Under the right conditions, these can depolymerize and go back to normal, but as the RBC continues to make repeat journeys around your body, this process accumulates. So the hemoglobin form polymers. The RBC membrane is deformed and pushed out like this and eventually becomes sickle-shaped. These sickle cells are fragile and prone to being crushed while in circulation, which can lead to anemia. The more severe issue with this disease is that sickle cells are more likely to form clots, and the disease can thus present with so-called vaso-occlusive crises of any area in the body. Now let's have a look at some enzyme-related anemias. As we know, RBCs don't have nuclei or mitochondria. They are required to make energy anaerobically, and they do this via the pathways of glycolysis and the pentose phosphate pathway. One of the enzymes required for the latter is called glucose 6-phosphate dehydrogenase, or G6PD for short. Any deficiency in G6PD will cause the RBC to be under increased risk of homolysis due to excess oxidative stress. Let's go into that a bit further. Glidothion is an antioxidant molecule which mops up excess free radicals in cells. NADPH is a molecule that's required to keep glutathione in a state where it is capable of this. G6PD helps produce NADPH from NADP, so without enough of this enzyme, we lack sufficient defense from a build-up of things that cause oxidative stress. Pyruvate kinase catalyzes the last step of glycolysis, which is also the last point at which synthesis of ATP occurs. Reduced ATP levels reduce the amount of energy available to the cell and causes a raft of problems, which eventually lead to breakdown of the RBC. With this deficiency as well, the level of anemia depends on the severity of the deficiency. Before we wrap up, we'll briefly touch on the two classifications of autoimmune hemolytic anemia. These are caused by RBC antigens being recognized as foreign by certain antibodies. RBCs are thus tagged prematurely for destruction. So-called warm hemolytic anemia is mostly idiopathic, but has certain associations with chronic inflammatory diseases. You can think warm, inflamed, there's a connection there, such as lupus, rheumatoid arthritis, the inflammatory bowel diseases, and also with white blood cell cancer. Cold hemolytic anemia can be caused by infection, by mycoplasma infection, EBV, syphilis, the list goes on, and is precipitated by reduced body temperature. So there you go, seven types of hemolytic anemia. I hope you enjoyed that. Stick around for our next video on how to diagnose hemolytic anemia. Thanks for watching this one. Hit subscribe, and we'll see you next time.