RED BLOOD CELL HISTOLOGY

One of the hardest things about hematology is interpreting pictures of red blood cells. There are seemingly a hundred different causes of anemia! I thought that the usual textbooks were subpar on this subject, so I made these diagrams to help you understand some of the classic shapes of these tricky guys! In no particular order...

 Let’s start from the beginning. The RBC is born inside of the bone marrow, dividing away from a hematopoietic stem cell. It matures in the marrow for a few weeks, building up hemoglobins and making adjustments to its genetic material. But before the RBC can leave the marrow, the nucleus has to  be ejected. Once all the nucleic acid is gone, the RBC can slip out into the circulation, where it will remain for the remainder of its brief lifetime, roughly 120 days. RBCs are a bit like wind up toys that the bone marrow sends out into the body. Once the RBC reaches old age, it starts to express surface proteins that signal its old age, like retired veterans proudly displaying their hard-earned war medals. Macrophages in the spleen notice those proteins, and gobble up the old farts.

So what exactly is a hemoglobin? Each hemoglobin is made up of 4 heme’s and 4 globins. The globin is a bulky protein that plays a scaffolding function (globin is greek for ball). Its job is to hold a single molecule of heme. The heme consists of a protoporphyrin ring (fun fact: the ring is responsible for the color of blood) with an iron in the center. Here’s a diagram of a typical hemoglobin (¼ of it, anyways): 

Why do we need hemoglobin? While gasses can dissolve into fluids (that’s how fish access oxygen), fluids can only absorb a finite amount of gas (the saturation point). But the body requires far more oxygen than this. So nature evolved a clever work around -- it fills the blood with proteins that are capable of temporarily binding to oxygen. Like a bus, hemoglobin grabs oxygen at the lungs, then carries it to its final destination in the tissues. 

How does hemoglobin know when to pick up oxygen and when to release it? It turns out that this is a fundamental question with hemoglobin. Hemoglobin has the ability to “wiggle” between two different shapes. In its “relaxed” shape it likes to bind oxygen, and in the “taut” state it doesn’t. And the cause of this change? Confusingly enough, it’s the presence of oxygen! When the RBC reaches the lungs, one oxygen molecule will bind to one molecule of iron, but doing so subtly alters the geometry of the protoporphyrin ring. This tiny change has an effect on the 3 neighboring hemes and globins. The other irons develop a stronger molecular attraction towards oxygen, hungrily gobbling up the free floating oxygens. This is called cooperative binding, and it’s a lot like peer pressure! The RBC eventually reaches its destination, deoxygenated tissues, which pull the oxygen away. And once again, we see peer pressure. When one molecule of O2 departs, it creates a conformational change that encourages the 3 neighboring peptides to let go of their oxygens. And the cycle repeats. It’s kind of brilliant when you think about it. There are a few other factors that can impact the “wiggliness” of hemoglobin, but these will be discussed further in the respiratory chapte