Ride the Red Road :

The Journey Within the Red

Blood Cell

By: Diana Pena-Moreno

Table of Contents

Overview Who Discovered the RBC? In 1658, a young Dutch scientist named Jan Swammerdam who used an early microscope to study blood cells from a frog. Anton van Leeuwenhoek, unaware of Swammerdam’s work, later proposed another microscopic description of RBC, this time with more precise descriptions and even approximating their size, "25,000 times smaller than a fine grain of sand". Later on in 1901, Karl Landsteiner published his discovery of the three main blood groups—A, B, and C (which he later renamed to O). A year later Alfred von Decastello and Adriano Sturli, two colleagues of Landsteiner, identified a fourth blood group (AB). In 1959, by use of X-ray crystallography , Dr. Max Perutz was able to reveal the structure of hemoglobin, the protein that enables RBCs to carry O2.

In our blood, hemoglobin is responsible for transporting oxygen. It consists of four proteins and the red pigment heme. Hemoglobin thus is the reason for the red color of blood. In the lungs, the hemoglobin's are loaded with oxygen, which they then transport to the cells of our body. The image shows an enlarged detail of hemoglobin with the oxygen-carrying pigment heme shown in pink. Red blood cells live about 120 days in the circulatory system. Is blood thicker than water? Blood is about twice as thick as water, thanks to all the cells and other bits that float in it. Why are red blood cells shaped like breath-mint disks with a dent in the middle? The breath-mint design allows cells to twist through capillaries, the tiniest blood vessels. A sphere or cube is less flexible and might get stuck. Also, the dents in the cells add to the surface area, allowing more oxygen and carbon dioxide to pass in and out of the cell. Red Blood Cells, for instance, have disliked flattened membranes. This shape gives them a maximum amount of surface area while still remaining smooth enough to slide through the smallest capillaries. Because red blood cells are manufactured for limited-time use, they have lost nearly all of their internal organelles, including nuclei.

Leeuwenhoek

Karl Landsteiner

Contents of the RBC. The Process of a RBC (Life Cycle) The RBC is produced in the red bone marrow and goes through a process called “erythropoiesis”. After the decreased O2 stimulates the RBC into circulation, it’s detected by the kidneys which then releases the hormone “erythropientin”. Stem cells in the red bone marrow called “hemocytoblasts” give rise to all of the formed elements in blood. If a hemocytoblast commits to becoming a cell called a proerythroblast, it will be developed into a new red blood cell. When matured, these cells live in blood circulation for about 100 to 120 days. At the end of their lifespan, they become senescent(old), and are removed from circulation. An average RBC lives for about 120 days. Every second 2.5 million RBC's are destroyed. Although this represents only 0.00001% of the total 25 trillion cells, these cells must be replaced if homeostasis is to be maintained. Our bones are constantly producing RBCs replacing the senescent ones, so you don’t ever have to worry about low blood supply.

The RBC is rather a strange cell because it lacks all organelles. It had a nucleus but as it grew to become fully functional in our blood stream, a RBC’s nucleus was extracted. Also, since the RBC doesn’t have a nucleus, it couldn’t divide or synthesize new cells.. Because of this, the cells degenerate due to aging or damage.

What Makes a RBC red? A RBC isn’t just red because it wants to be, it contains a substance called “hemoglobin”. Hemoglobin is a complex molecule that’s composed of iron and protein, it’s designed to hold oxygen and carry it to cells that need it. Since hemoglobin contains iron, it makes it excellent for transporting oxygen and carbon dioxide. After it does that, the empty hemoglobin molecules bond with the tissue's carbon dioxide or other waste products and removing it away.

The Shape and Structure of the RBC

The RBC Membrane Composition

The RBC Membrane has basically 3 parts, cytoskeletal network (8%), a lipid bilayer (40%), transmembrane proteins (52%).

• Cytoskeleton Network:

• The Lipid Bilayer: The red blood cell’s membrane consist a typical lipid bilayer. This lipid bilayer is composed of cholesterol and phospholipids in equal proportions which is determined by weight. The lipid composition is important because it characterize many physical properties such as how permeable and fluid the membrane can be. The activity of many membrane proteins is directed by the interactions with the lipids in the bilayer. Unlike the cholesterol which are evenly distributed between the inner and outer layers, the five major phospholipids are asymmetrically placed.

• Transmembrane Proteins: The proteins of the membrane skeleton are responsible for the , flexibility, deformability, and durability of the RBC, enabling it to squeeze through veins and capillaries that are less than half the diameter of the red cell itself, and recovering it’s circular shape as soon as the cells stop receiving compressive forces. Impressively, there are currently more than fifty known membrane proteins. Approximately 25 of these membrane proteins carry antigens( a toxin substance that induces an immune response in the body; the production of antibodies). These membrane proteins can perform a wide diversity of tasks, such as transporting ions and molecules across the red cell membrane, adhesion and interaction with other cells. The red blood cell membrane proteins are organized according to their function.

The RBC “Vertical interaction” helps stabilize the lipid bilayer membrane,

while the “Horizontal interaction” support structural integrity of RBC and having enough surface area to hold the hemoglobin. They are basically a biconcave disc with a depressed center on both sides. . These depressed centers allow the cells to have more cell membrane surface which can be exposed to diffusing oxygen while transiting the lungs. This unique shape allows the RBC to be more flexible when moving through tight passages

Journey of the RBC Why is this trip of the RBC so crucial? The certain veins, ateries, and capillaries guide the RBC to certain parts of our body in an orderly manner, in a way that the paths wouldn’t get blocked so our blood delivers the O2 in time.

This journey takes about 1-3 minutes for the blood to circulate around our body depending on our heart rate.

We all know RBCs travel around us, but let’s just look at it’s route. Did you ever wondered about this? 1) The deoxygenated red blood cell travels to the heart in the vena cava 2) It then enters the right atrium 3) The right atrium then contracts and pushes it through the tricuspid and into the right ventricle 4) The right ventricle contracts and pushes it out of the heart through the semi lunar valve 5) It travels through the pulmonary artery then to the lungs, here it picks up oxygen 6) It then travels back to the heart through the pulmonary vein and enters the left atrium 7) the left atrium contracts and pushes it through the bicuspid and into the left ventricle 8) the left ventricle contracts and pushes it through the semi lunar valve out of the heart and into the Aorta. 9) They travel through the Aorta and into the kidneys, trunk and lower limbs. 10) Then the de-oxygenated blood travels up through the Vena Cava and then the travels start again.

Damage Control Damage control is when our blood responds to an injury or infection. If it was an infection, the our white blood cells would fight it off. But if it was an injury, our blood must clot. The process by which blood clots at the right time, but doesn't clot when it doesn't need to is called hemostasis. Hemostasis- When you are cut, your blood vessels are cut, and you bleed. You don't bleed to death, but instead, the blood stops flowing when you get a clot. Actually, a lot more than just a clot occurs. • When a blood vessel is cut, it is a good thing for it to

contract (tighten)... that prevents excessive blood loss from the cut vessel because less blood will be flowing through that vessel. The contraction of a blood vessel is called blood vessel spasm.

• The cut end of the contracted vessel is still an area that could leak blood. So, the open end has to get plugged up. This happens with the action of platelets, and it is called a platelet plug.

• Plugs are not long-term items. They are just “temporary-fixes." How do we get a more lasting blockage? With clotting, which is also called blood coagulation.

• Once the clot has formed, it needs to tighten up. The platelets constrict and pull the clot more tightly, called clot retraction. Simultaneously while the blood vessel needs to begin its repair.

• In order to completely regenerate, the clot eventually has to be removed as the blood vessel repair is done. Clot removal is called fibrinolysis.

• Blood Vessel Spasm- If you cut through a muscle, what remains contracts. Smooth muscles are in the wall of the blood vessel so, the smooth muscles contract right away. This happens immediately, occurring at the moment of the injury. It won't last forever, this vasospasm, but it lasts long enough for the platelet plug to happen. And since platelets secure serotonin, the serotonin forces muscle to contract, when the platelet plug forms, the vasoconstriction caused by the vasospasm continues for a much longer period.

• Platelet Plug- A platelet plug is formed when platelets are exposed to an environment they don’t normally see.When a cut/injury is made, platelets come zooming out of the blood vessel and run head on into collagenous fibers. And, all of a sudden, they change forms completely, they go from being smooth little cellular pieces, to being sticky, pointy, rough chunks of cells. Change in appearance is not their only change. As they change the way they look, they change to start actively secreting serotonin. They also get very sticky, and start clumping up together. As more and more stick together, they form a huge, sticky clump which is the platelet plug.

• Coagulation- Clotting is what makes the blood loss stop for a long period of time. The final action that completes the clot is based in a chemical change of fibrinogen, one of the blood plasma proteins. Fibrinogen is one of the plasma proteins, and it is dissolved in the plasma. But, when blood needs to clot, a chemical reaction of the fibrinogen occurs. Fibrinogen gets changed in this chemical reaction into fibrin. Fibrin, unlike fibrinogen, is not able to dissolve in the plasma. Sine fibrin is a thread-like protein, when enough of it forms, it ends up sticking together in a mesh-like net, this mesh is tight enough to prevent other materials from flowing through it. The fibrin threads and the platelets stuck in it forms into a clot.

Disease Control Cont. Inflammation With the next injury/infection you get, a reaction called the inflammatory reaction occurs. This is when an inflammation happens and that produces an area to look swollen. This happens because in order to get rid of an infection and/or the cellular debris from an injury, you need macrophages, neutrophils, and you even need lymphocytes (to fight the infection with an immune response). Even eosinophils can destroy some bacteria on occasion. These are all white blood cells. When tissues get harmed, the damaged cells are like chemical alarms. They release their cell contents, which are chemicals, and these chemicals are impulses for other cells. There are cells in the connective tissue, mast cells, that release histamine when they recognize the chemicals of damaged cells. This gets the inflammatory reaction going.

Histamine causes the nearby blood vessels widen to bring more blood around to the damaged area. The mast cells don’t release a lot of histamine, but as more blood starts to come through the area, that means that more white blood cells will reach the wounded tissue. The basophils that enter the area will also release histamine, and this brings the inflammatory response into full power, because all the blood really gets flowing into the wounded area, and many white blood cells enter the wounded tissue. All those white blood start doing their part in this process. Even plasma will do their part on clotting the wound, clotting tends to happen around the area of inflammation (but not in it), preventing further spread of the infection.

Blood Shot Eyes I’m quite sure that in some time in your life, your eyes have gotten red and you wonder why that happens? Well this occurs when the small blood vessels on the surface of the eye become swollen and clogged with blood. This is caused by lack of oxygen to the cornea or the tissues near the eyes. Normally, bloodshot eyes are not really a major concern but if eye pain or impaired vision occurs, that may be a serious problem.

What is Eye Inflammation? An eye inflammation generally occurs as a reaction to viral or bacterial infection, environmental irritants like pollen, allergies, etc.. In most occasions, eye inflammation aren’t serious, it is important to control the severity of the inflammation. Because the eyes are such delicate organs, even a small amount of scar tissue can cause permanent visual impairment.

Red Blood Cell Count

The RBC count is a blood test that determines the number of red blood cells in a taken sample. This test also take a look at the shape and the size of the RBCs. All of this information is later used to see the number of RBCs per microliter of blood. Since everyone is different, the RBC count value alter due to the age and sex of the patient. For women, the RBC count ranges from 4.2-5.0 million red blood cells per microliter and 4.6-6.0 per microliter for men. For children the ranges are normally from 3.8-5.5 million RBC per microliter. This test is very important to the patient’s health because it is a good indicator of their health. If the patient had low red blood cell count, that might mean the patient has anemia, acute or chronic blood loss, malnutrition (lacking nutrition), chronic inflammation, or other disorders that can affect them. An increase of red blood cells can also happen naturally, though. People who live at high altitudes tend to have a higher-than-average RBC count, and smokers generally have a higher number of red blood cells than non-smokers.

Complete Blood Count

(CBC) The CBC test is used as a broad screening test to check for disorders like anemia, infection, or any other disease that is in the blood. It is actually a series of tests that examines different parts of the blood. The CBC test also tells you the number, size, volume, and hemoglobin content of red blood cells

^Here shown is a patient getting their RBC count.

High Hemoglobin Count

Like the RBC count, the High Hemoglobin Count evaluates the above-average concentration of oxygen-carrying proteins in your blood. Hemoglobin count (hemoglobin level ) indicates the RBC’s blood's oxygen carrying capacity.

This test is slightly different from a high red blood cell count, because of the varying amount of hemoglobin in each cell. You could have a high hemoglobin count even if your red blood cell count falls within the normal range.

Same as the RBC count, for a high hemoglobin count is slightly different from one medical patient to another. The defintinon for hemoglobin is determined by sex and age. For men, the hemoglobin is defined as more than 17.5 grams (g) of hemoglobin per deciliter (dL) of blood and 15.5 g/dL for women. The definition of high hemoglobin for children varies with age and sex.

Diseases • Thalassemia- is a genetic disease that results in the production of an abnormal ratio of hemoglobin subunits.

• The malaria parasite spends part of its life-cycle in red blood cells, feeds on their hemoglobin and then breaks them apart, causing fever. Both sickle-cell disease and thalassemia are more common in malaria areas.

• Polycythemias (or erythrocytoses) -are diseases characterized by a abnormal increase of red blood cells. In polycythemia, the increased number of red blood cells results from an abnormality in the bone marrow.

• Hemolysis- the general term for excessive breakdown of red blood cells. It can have several causes and can result in hemolytic anemia.

• Hemolytic Anemia- Hemolytic anemia is a condition in which there are not enough red blood cells in the blood, due to the premature destruction of red blood cells.

There are several diseases that affect the RBC and can be fatal. Here listed are some:

• Anemia- are diseases characterized by low oxygen transport capacity of the blood, because of low red cell count or some abnormality of the red blood cells or the hemoglobin.

• Iron Deficiency Anemia- the most common anemia; it occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed

• Sickle-cell Anemia- is a genetic disease that results in abnormal hemoglobin molecules. When these release their oxygen load in the tissues, they become insoluble, leading to mis-shaped red blood cells. These sickle shaped red cells are less deformable and are viscoelastic, meaning they have become rigid and can cause blood vessel blockage, pain, strokes, and other tissue damage.

Sickle Cell

Treatments

• Thalassemia- Like the other illnesses, treatments for thalassemia depends on the type and severity of the disorder. Patients who have alpha or beta thalassemia trait have mild or no symptoms, they don’t really need treatment .If your disease is moderate or severe, the standard treatment is blood transfusion. This process takes about 1-4 hours. During a blood transfusion, a needle is inserted into one of your blood vessels. Through this line, you receive healthy blood.

Iron Chelation Therapy- Because hemoglobin in RBCs are made up of iron-rich protein, regular blood transfusions can result to a buildup of iron in the blood. This condition is called iron overload. Iron overload damages the liver, heart, and other parts of the body. Iron chelation therapy is used to prevent this condition, it remove excess iron from the body.

• Polycythemias- Since Polycythemia is a chronic condition that can't be cured, Treatments are trying to reduce the amount of RBCs that you have. Treatment can prevent complications from polycythemia and can eliminate the disease's signs and symptoms. Taking blood out of your veins is a common treatment for patients with Polycythemia, taking a certain amount of blood out of your veins in a procedure called phlebotomy . This treatment reduces the number of blood cells and the volume in your blood. How often you need phlebotomy depends on the severity of your condition. Depending on how severe your diseases is will determine how often you’ll get phlebotomy.

• Medicine- Patients that couldn’t be helped phlebotomy alone are recommended medicines such as hydroxyurea or anagrelide to restrain your bone marrow's ability to produce blood cells. Another medicine is Interferon-alpha, it may be used to stimulate your immune system to fight the overproduction of RBCs.

Hemolytic Anemia- Blood transfusions are used to treat severe or life-threatening hemolytic anemia. Sometimes, medicines can improve some types of hemolytic anemia, especially autoimmune hemolytic anemia (AIHA). Corticosteroid medicines, such as prednisone, can limit your immune system’s ability make antibodies (proteins) against red blood cells.

Plasmapheresis- Plasmapheresis is a procedure that removes antibodies from the blood. The plasma, which contains the antibodies, is separated from the rest of the blood. Then, plasma from a donor and the rest of the blood is put back in your body. This treatment may help if other treatments for immune hemolytic anemia don't work.

Blood Transfusion A blood transfusion is a common procedure in which blood is given to you through an intravenous (IV) line in one of your blood vessels. Transfusions require careful matching of donated blood with the recipient's blood.

Anemia- due to many types of anemia, the treatments will vary. Iron Deficiency Anemia- Depending on if you’re not consuming enough iron(iron increase intake); not absorbing iron (surgery), or losing small amounts of iron overtime from anything like alcohol. Doctors will often recommend foods that contain a lot of iron (seafood, dried fruits, lima beans, whole grains, green leafy vegetables and blackstrap molasses) or iron pills. But if the case is more severe, like if it was caused by blood loss, surgery, transfusions, or hormone injections may be recommended. Sickle-Cell Anemia-There really isn’t a cure to sickle cell anemia, but the treatments available are to relieve symptoms and treat complications. The treatments that are recommended to a patient are suppose to relieve pain, prevent infections, organ damage, and strokes, and control complications (if they occur). Blood and marrow stem cell transplants may help cure sickle cell anemia for a few of people. Scientists are still trying to discover ways to cure anemia. Treating pain- Mild pain is often treated with over-the-counter medicines, heating pads, water, and rest. If the patient is in severe pain, they may need to be treated in a day clinic, emergency room, or hospital. Fluids, medicines, and O2 therapy are used to treat patients with acute pain. Your doctor may prescribe antibiotics if you have an infection. Hydroxyurea Hydroxyurea can treat severe sickle cell anemia .This medicine help starts your body to make fetal hemoglobin. Fetal hemoglobin is the type of hemoglobin that newborns have. Fetal hemoglobin helps prevent red blood cells from sickling and improves anemia. It is proven that Hydroxyurea helps improves a person’s health. Doctors and scientists are trying to extend its effect. But this also has a downside, hydroxyurea can reduce the number of white blood cells in your blood and that can lead to serious infections. This is a fatal risk that’s taken, patients who take hydroxyurea need to be careful on their follow ups. Blood and stem cell transplants or gene therapy There’s a lot of complications if a patient has sickle cell anemia, like stroke, infections(fatal), or eye damage.

Blood Donors Blood Testing • If a donor’s blood is going to be used to transfusion, the type of blood must be

determined. More testing, including a crossmatch, is usually done before a transfusion. Group O is often known as the "universal donor “ because it works well with all of the other blood types, but this only refers to red cell transfusions. Most blood is tested for diseases like STDs. Donated blood is tested by many methods, but the core tests recommended by the World Health

The process of blood donation starts when a person voluntarily offers his/her blood for transfusions or made into medications by a process called fractionation. Most blood donors are unpaid volunteers who give blood for a community supply. Many donors donate blood as an act of charity and kindness, but some are paid. A donor can also have blood drawn for their own future use. Donating is relatively safe, but some donors have bruising where the needle is inserted or may feel faint. Different Types of Donation- An allogeneic donation is when a donor gives blood for storage at a blood bank for transfusion to an unknown recipient. A directed donation is when a person donates blood for transfusion to a specific individual.

A replacement donor donation is a hybrid of the two types above and is common in developing countries. In this case, a friend or family member of the recipient donates blood to replace the stored blood used in a transfusion, ensuring a consistent supply. Blood that is used to make medications can be made from allogeneic donations or from donations exclusively used for manufacturing.

Blood is sometimes collected using similar methods for therapeutic phlebotomy. This blood is sometimes treated as a blood donation, but may be immediately discarded if it cannot be used for transfusion or further manufacturing.

Lab Grown RBCs.

In 2008, the first successful transfusion of artificial blood into a human, Luc Douay, of Pierre and Marie Curie University, Paris. He extracted hematopoietic stem cells from a volunteer patient’s bone marrow, and added a whole lot of other growth factors. Douay's team then injected 10 billion of them (equaling 2 milliliters of blood) back into the marrow donor's body. This is exciting news for international health care. "The results show promise that an unlimited blood reserve is within reach," says Douay. Even with the rise of donor numbers, the world is in pressing need of a blood. . The difficult step was to induce the cells to eject their nucleus; this was achieved by growing the cells on stromal cells (cells that are connective tissue cells of an organ found in the loose connective tissue) from the bone marrow. Many scientists and biologists hope that these manmade cells can be used to blood transfusions.

Rouleaux

Rouleaux is a condition when RBCs stack

together in long chains. This is known as "rouleaux formation" and it happens when serum proteins increase, particularly fibrinogen and globulins. This is the mechanism for the sedimentation rate, which increases non-specifically with inflammation and increased "acute phase" serum proteins. This is an unhealthy state because the cells aren’t capable of absorbing and carrying oxygen. It is a pre-cursor to many serious diseases. Treatments: Treatment for rouleaux varies from natural remedies, like nutritional supplements, to ozone therapy. Ozone therapy prevents rouleaux formation, in this type of therapy, a mixture of ozone and oxygen is managed by intramuscular injection, through the rectum, or intravenously. If the patient is getting the injection intravenously, then s some of the patient's blood would have to be removed, treated with the oxygen and ozone mixture, and then reintroduced into the patient.

How to Stay Healthy

Now, it’s pretty clear how a small blood cell can make such a big difference, without it, you will die slowly and painfully. There are plenty of ways to stay healthy and keep yourself in good shape.

Exercise, its good for you and it energizes your circulatory system so your heart rate will increase to get all those RBC circulating around yourself quite quickly.

Let Me Tell You Something You Didn’t Know.

• The body makes about two million red blood cells every second.

Glossary

Citations

• Sites: http://faculty.stcc.edu/AandP/AP/AP2pages/Units18to20/blood/redblood.htm

• http://www.mayoclinic.com/health/high-hemoglobin-count/MY00112

• http://www.fi.edu/learn/heart/blood/red.html • http://en.wikipedia.org/wiki/Red_blood_cell

• Pictures: • http://www.ajpip.com/images/foh2/bld/roul

eau2.jpg http://upload.wikimedia.org/wikipedia/commons/thumb/b/b9/Blutspende_Piktogramm.GIF/220px-Blutspende_Piktogramm.GIF • http://www.sciencephoto.com/image/30394

4/large/P2060524-Artery_and_red_blood_cells-SPL.jpg

• http://faculty.stcc.edu/AandP/AP/imagesAP2/blood/platelets.jpg

• http://www.fi.edu/learn/heart/blood/images/red-blood-cells.jpg

• http://www.ajpip.com/images/foh2/bld/normal2.jpg

• http://themedicalbiochemistrypage.org/images/hemoglobin.jpg