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...
RED BLOOD CELLS
Erythrocytes
Red Blood Cells (RBCs) are the abundant, red, anucleate cells that constitute the bulk of your blood. Their one job in life is to ferry oxygen from the aerated lungs to the hungry tissues (they also shuttle CO2 and help with some metabolic reactions, but those jobs are less important). The RBC’s active ingredient is a metallic-protein molecule called a hemoglobin (Hgb). There are thousands of Hgbs inside each RBC.
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
And here’s an incredibly complex metaphor that compares Hgb to a delivery truck.
There are a few different types of hemoglobin. They differ by their globins, which can be either alpha, beta, gamma or delta. Different rearrangements of globins will determine our flavor of hemoglobin. This is mostly important because of Thalassemia, see below.
ANEMIA
An- (without) -emia (blood)
Anemia refers to the loss of Hgb and/or RBCs. Anemia is defined quantitatively. The Hgb lab test must be low (under 12 in women and 13 in men).
First let's talk about symptoms. Mild anemia is usually asymptomatic. But as the Hemoglobin (Hgb) starts to dip, vague symptoms will manifest. Patients (in real life) may not have every single one of these symptoms, but rather a blurry collection of some of them. The most obvious symptom is skin pallor. The other symptoms of anemia are caused by the lack of oxygen carrying capacity. A sort of global functional hypoxia. Look for fatigue, lightheadedness, SOB and might even have chest pain. Another sign is tachycardia, which is only partially explained by the functional hypoxia. The tachycardia is also caused by a property of fluids! Blood is chock full of RBCs, but anemic patients will have less RBCs in their plasma, and so the blood will be thinned out. This drop in viscosity makes the blood more like water than honey. This property enables the heart to pump really fast, which it’s going to try to do because of the decreased oxygenation of the tissues.
Now let’s consider the physical exam. Skin pallor is kind of subjective. Maybe they’re just really pale! Or maybe they’re a person of color, in which case pallor is less obvious. Enter one of my favorite exam tests: conjunctival pallor. Put your finger on their bottom eyelid, and pull down, exposing the bottom of the eyeball and the palpebral conjunctiva. There should be a pinkish rim, but this is absent with severe anemia.
How do we test for anemia? There’s no perfect single lab test for anemia. But most clinicians rely on the Hemoglobin and Hematocrit (H&H) tests. Most physicians tend to prefer one or the other, but either test works. They are mathematically derived from one another -- just multiply the Hgb by x3 to get the Hct. There are a few other labs that help us investigate the anemia a little bit further. Start with the MCV (mean corpuscular volume), a lab test that measures RBC volume. This will help us organize all of the anemias. They will either be small (microcytic), normal (normocytic) or large (macrocytic).
ANEMIA FLOWCHART
Some hemolytic conditions (Sickle Cell) are both intra- and extravascular. Oh well.
¯\_(ツ)_/¯
