RBC Conditions

Now that we know the basic players of hematology we’re going to dive into diseases and things that can go wrong with different types of cells. Every type of cell can go haywire in all types of combinations. Conditions, symptoms, and lab findings blend together, so it’s also important to understand why things are happening on a molecular level because if you know the root of the problem, you can better understand the manifestation of the problem.

RBC conditions:
RBCs can go haywire! Earlier we went through problems with hemoglobin. RBC survival and function is dependent on three things: the plasma membrane, the structure and function of hemoglobin, and specific metabolic pathways. We will focus on the most important conditions and break down complex concepts.

Anemia:
Anemia is the inability of blood to supply adequate oxygen to tissue. Anemia is very common, can often be secondary to other diseases, and comes in many forms. Let’s break down a few of the more common types.

Iron deficiency anemia:
As you may recall from above, hemoglobin requires iron and to be more specific heme requires iron. Lack of dietary iron, excessive blood loss, and iron absorption and reutilization issues can all cause iron deficiency anemia.

Sideroblastic anemia:
Sideroblastic anemia is a condition where sideroblasts (abnormal RBCs with trapped iron) are detected in the bone marrow. Sideroblastic anemia can be inherited genetically or acquired through things like drug toxicity and lead poisoning. In the case of genetics, they mostly revolve around defective enzymes involved in protoporphyrin ring synthesis. Not only can the heme molecule not be formed but the unused iron can become trapped in the mitochondria. Help! Let me out, I’m stuck in the mitochondria!

Pernicious anemia:
Pernicious anemia is related to a vitamin B12 deficiency, and more specifically, the inability to absorb vitamin B12 due to lack of intrinsic factor (IF). IF is a protein produced by stomach parietal cells and is involved in the absorption of vitamin B12 through the intestine. Decreases in IF can be due to an autoimmune problem or can be genetic. The absorption of vitamin B12 is important because it is required for DNA synthesis and can cause pancytopenia where all cell lines are affected.

Nerdy Note
The word pernicious means “deadly,” and up until the 1920’s pernicious anemia was fatal. It was in the 1920’s that a scientist, George Whipple (1878-1976), ran experiments that showed dogs that were bled to be anemic recovered quickly by eating raw liver. Liver and liver juice was then given to pernicious anemia patients and it fixed their problem; however, this was by coincidence. It was later found the large amounts of iron in the liver and liver juice helped the anemic dogs recover, and it was by coincidence that the liver and liver juice contained vitamin B12 and helped pernicious anemia patients get well. The reason for this is the liver of humans and animals contains a few years of stores of vitamin B12. Once this discovery was made, people with pernicious anemia ate liver and liver juice in fairly high quantities. In the late 1920’s liver juice extract (~75x stronger than liver juice) was created to eliminate the unpleasantness of ingesting liver and liver juice. It wasn’t until 1948 that the component of liver juice responsible for the cure of pernicious anemia was found to be cobalamin, aka vitamin B12.

Megaloblastic anemia:
A megaloblast is defined as a large abnormally developed RBC. Megaloblastic anemia is mostly morphology related and is generally caused by vitamin B12 and/or folic acid deficiency. Both of these deficiencies lead to DNA synthesis defects and increased red cell size due to the defects. Common findings in megaloblastic anemia are low hemoglobin, increased MCV, normal MCHC (normochromic), macro-ovalocytes, and hypersegmented neutrophils.

Microangiopathic hemolytic anemia:
In this condition, RBCs become fragmented as they come in contact with fibrin strands. This type of anemia is seen in coagulation conditions like DIC and TTP where large amounts of coagulation factors are used. Typical RBC abnormalities seen are schistocytes due to RBCs running into fibrin and NRBCs because more mature RBCs are needed than available causing immature NRBCs to enter circulation in larger amounts than normal.

Red cell inclusions:

Howell Jolly bodies:
Howell Jolly bodies are nuclear fragments containing DNA. They can be seen in a number of different conditions but most noteworthy is post splenectomy. In normal circumstances the spleen will remove these inclusions but in times of stress or if you no longer have a spleen, these inclusions can be present. They can also be found in thalassemia, hemoglobinopathies, and megaloblastic anemia.

Heinz bodies:
Heinz bodies are denatured precipitated hemoglobin. They can be seen in thalassemia as well as G6PD deficiency (G6PD is a red cell enzyme involved in hemoglobin function). Heinz bodies need special staining to be visible (not visible on Wright stain). They can be viewed using the supravital stains crystal violet and brilliant cresyl blue.

Pappenheimer bodies:
Pappenheimer bodies and siderotic granules are basically the same thing. They are small clusters of excess iron that can be distinguished through staining. Pappenheimer bodies can be detected using a Wright stain and siderotic granules using a Prussian blue stain. The difference in stains is because the Wright stain stains the protein matrix and Prussian blue directly stains the iron granules. They can most commonly be seen in hemoglobinopathies, sideroblastic anemia, and post-splenectomy.

Vocabulary Note
Mature RBCs containing siderotic granules are termed siderocytes. Nucleated RBCs (immature RBCs) containing siderotic granules are termed sideroblasts.

Basophilic Stippling:
Basophilic stippling are dots of residual RNA that can be present in conditions like thalassemia and lead poisoning. They appear all over the cell.

Cabot Ring:
Cabot rings are remnants of the mitotic spindle. They can be seen in megaloblastic anemia.

Malaria:
All four species of malaria can invade RBCs. They can be detected on a peripheral smear in ring or troph form using a Giemsa stain.

Babesia:
Babesia microti is another parasite that can infect RBCs. It can be ring shaped and appear like malaria. One big difference in distinguishing it from malaria is Babesia can be found outside of the RBC in the blood circulation. It is commonly transmitted through ticks.

Other RBC conditions:

Hereditary spherocytosis:
Hereditary spherocytosis is a familial disorder associated with mutations in RBC membrane proteins. The mutation causes decreased deformability of the RBC which makes it prone to hemolysis (more likely to break). Spherocytes cause an increased MCHC (due to the smaller size), an increased osmotic fragility test, extravascular hemolysis, and autoimmune hemolytic anemia.