PDF | Erythropoiesis occurs mostly in bone marrow and ends in blood stream. Mature red blood cells are generated from multipotent. Red blood cells (RBCs) are vital for oxygen delivery to tissues and constitute the vast majority of all cells in blood. After leaving the red bone marrow as mature. Stem cells are multipotential cells (capable of developing into different types of blood cells). Some stem cells enter the blood and circulate. Red blood cells carry .
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ultimately banned at the end of the 17th century. Around the time that such transfusions were being banned the red blood cell (RBC) became a focus of scientific. The erythrocyte, commonly known as a red blood cell (or RBC), is by far the most common formed element: A single drop of blood contains millions of. PDF | 2 hours read | Significance: Recent clinical evidence identified Keywords : red blood cells, nitric oxide, anemia, RBC deformability.
Received Mar 20; Accepted Apr 7. This article has been cited by other articles in PMC. Abstract The most important function of red blood cells RBCs is the carrying of oxygen, but they are also involved in inflammatory processes and during coagulation. RBCs are extremely deformable and elastic, as they are exposed to shear forces as they travel through the vascular system. In inflammatory conditions, and in the presence of hydroxyl radicals, RBCs loose their discoid shape.
In response to the hypoxemia, the kidneys secrete EPO to step up the production of erythrocytes until homeostasis is achieved once again. To avoid the symptoms of hypoxemia, or altitude sickness, mountain climbers typically rest for several days to a week or more at a series of camps situated at increasing elevations to allow EPO levels and, consequently, erythrocyte counts to rise.
When climbing the tallest peaks, such as Mt. Everest and K2 in the Himalayas, many mountain climbers rely upon bottled oxygen as they near the summit. Lifecycle of Erythrocytes Production of erythrocytes in the marrow occurs at the staggering rate of more than 2 million cells per second. For this production to occur, a number of raw materials must be present in adequate amounts. These include the same nutrients that are essential to the production and maintenance of any cell, such as glucose, lipids, and amino acids.
However, erythrocyte production also requires several trace elements: Iron. We have said that each heme group in a hemoglobin molecule contains an ion of the trace mineral iron. On average, less than 20 percent of the iron we consume is absorbed. Heme iron, from animal foods such as meat, poultry, and fish, is absorbed more efficiently than non-heme iron from plant foods. The bone marrow, liver, and spleen can store iron in the protein compounds ferritin and hemosiderin.
Ferroportin transports the iron across the intestinal cell plasma membranes and from its storage sites into tissue fluid where it enters the blood. When EPO stimulates the production of erythrocytes, iron is released from storage, bound to transferrin, and carried to the red marrow where it attaches to erythrocyte precursors. A trace mineral, copper is a component of two plasma proteins, hephaestin and ceruloplasmin.
Without these, hemoglobin could not be adequately produced.
Located in intestinal villi, hephaestin enables iron to be absorbed by intestinal cells. Ceruloplasmin transports copper. In a state of copper deficiency, the transport of iron for heme synthesis decreases, and iron can accumulate in tissues, where it can eventually lead to organ damage.
The trace mineral zinc functions as a co-enzyme that facilitates the synthesis of the heme portion of hemoglobin. B vitamins. Thus, both are critical for the synthesis of new cells, including erythrocytes. Erythrocytes live up to days in the circulation, after which the worn-out cells are removed by a type of myeloid phagocytic cell called a macrophage, located primarily within the bone marrow, liver, and spleen.
Hemoglobin that is not phagocytized is broken down in the circulation, releasing alpha and beta chains that are removed from circulation by the kidneys. The iron contained in the heme portion of hemoglobin may be stored in the liver or spleen, primarily in the form of ferritin or hemosiderin, or carried through the bloodstream by transferrin to the red bone marrow for recycling into new erythrocytes.
The non-iron portion of heme is degraded into the waste product biliverdin, a green pigment, and then into another waste product, bilirubin, a yellow pigment. Bilirubin binds to albumin and travels in the blood to the liver, which uses it in the manufacture of bile, a compound released into the intestines to help emulsify dietary fats. In the large intestine, bacteria breaks the bilirubin apart from the bile and converts it to urobilinogen and then into stercobilin.
It is then eliminated from the body in the feces. Broad-spectrum antibiotics typically eliminate these bacteria as well and may alter the color of feces. The kidneys also remove any circulating bilirubin and other related metabolic byproducts such as urobilins and secrete them into the urine.
The breakdown pigments formed from the destruction of hemoglobin can be seen in a variety of situations. At the site of an injury, biliverdin from damaged RBCs produces some of the dramatic colors associated with bruising.
With a failing liver, bilirubin cannot be removed effectively from circulation and causes the body to assume a yellowish tinge associated with jaundice. Stercobilins within the feces produce the typical brown color associated with this waste. And the yellow of urine is associated with the urobilins. The erythrocyte lifecycle is summarized in Figure 4. Figure 4. Erythrocyte Lifecycle. Erythrocytes are produced in the bone marrow and sent into the circulation.
At the end of their lifecycle, they are destroyed by macrophages, and their components are recycled. When the number of RBCs or hemoglobin is deficient, the general condition is called anemia.
There are more than types of anemia and more than 3. Anemia can be broken down into three major groups: those caused by blood loss, those caused by faulty or decreased RBC production, and those caused by excessive destruction of RBCs.
Clinicians often use two groupings in diagnosis: The kinetic approach focuses on evaluating the production, destruction, and removal of RBCs, whereas the morphological approach examines the RBCs themselves, paying particular emphasis to their size. A common test is the mean corpuscle volume MCV , which measures size. Normal-sized cells are referred to as normocytic, smaller-than-normal cells are referred to as microcytic, and larger-than-normal cells are referred to as macrocytic.
Reticulocyte counts are also important and may reveal inadequate production of RBCs. The effects of the various anemias are widespread, because reduced numbers of RBCs or hemoglobin will result in lower levels of oxygen being delivered to body tissues. Since oxygen is required for tissue functioning, anemia produces fatigue, lethargy, and an increased risk for infection.
An oxygen deficit in the brain impairs the ability to think clearly, and may prompt headaches and irritability. Lack of oxygen leaves the patient short of breath, even as the heart and lungs work harder in response to the deficit.
Blood loss anemias are fairly straightforward. In addition to bleeding from wounds or other lesions, these forms of anemia may be due to ulcers, hemorrhoids, inflammation of the stomach gastritis , and some cancers of the gastrointestinal tract.
The excessive use of aspirin or other nonsteroidal anti-inflammatory drugs such as ibuprofen can trigger ulceration and gastritis. Excessive menstruation and loss of blood during childbirth are also potential causes.
Anemias caused by faulty or decreased RBC production include sickle cell anemia, iron deficiency anemia, vitamin deficiency anemia, and diseases of the bone marrow and stem cells. A characteristic change in the shape of erythrocytes is seen in sickle cell disease also referred to as sickle cell anemia.
A genetic disorder, it is caused by production of an abnormal type of hemoglobin, called hemoglobin S, which delivers less oxygen to tissues and causes erythrocytes to assume a sickle or crescent shape, especially at low oxygen concentrations Figure 5.
These abnormally shaped cells can then become lodged in narrow capillaries because they are unable to fold in on themselves to squeeze through, blocking blood flow to tissues and causing a variety of serious problems from painful joints to delayed growth and even blindness and cerebrovascular accidents strokes.
Sickle cell anemia is a genetic condition particularly found in individuals of African descent. Figure 5. Diabetes also frequently occurs in hemochromatosis patients [ 15 ]. Interestingly, the pathophysiology of diabetes in hemochromatosis is thought to be due primarily to defects in the early insulin response to glucose [ 11 ]. This relationship was also found where higher serum ferritin level and higher heme iron intake is associated with elevated risk of diabetes [ 16 ]. Recently, we have shown that in diabetes, the RBC membranes have a changed roughness when using atomic force microscopy AFM [ 5 ].
Measurement of surface roughness showed a decrease in roughness and alterations in the cytoskeletal matrix and the connections between band 3 and 4 proteins and the matrix. Furthermore, AFM measurement of the macro-parameters indicated that erythrocytes in diabetes are smaller, with a reduced concave depth. Also, a changed superficial protein structure rearrangement was noted [ 5 ].
Scanning electron microscopy SEM has also shown that in inflammatory diseases like thrombo-ischemic stroke and diabetes, RBCs have a changed ultrastructure [ 10 , 17 ]. Previously, we have also shown that exposing RBCs of healthy individuals to iron, can also induce similar shape changes [ 10 ]. The changes were ascribed to the formation of hydroxyl radicals in experiments and the presence of these radicals in diseases conditions that ultimately lead to inflammation [ 18 ].
The question that now arises is whether ultrastructure can give us insights on how fast these changes may occur; and ultimately therefore, how adaptable these cells are. We know that RBC shape changes in diabetes, and when physiological levels of iron are added to healthy individuals.
Here we determine if such changes are also seen in hereditary hemochromatosis. Also, we investigate if addition of glucose to healthy whole blood will induce changes to these cells, and compare results to when iron is added to healthy whole blood.
The addition of iron and glucose was done to determine how fast RBCs can adapt in the presence of a changed environment.
Additionally, as it is known that the coagulation system is changed in the presence of iron overload, due to the generation hydroxyl radicals in particular, we also compare RBC shape changes in the presence of thrombin, that creates fibrin networks and dense matted deposits in inflammation [ 19 ].
Therefore, RBC changes, in the presence of iron and glucose with the addition of thrombin, as well as in diabetes and hemochromatosis also with and without the addition of thrombin were studied and compared to that of RBCs from healthy individuals.
Materials and methods Human subjects Ten non-smoking healthy individuals with no chronic diseases and who do not use any medication, were used as control subjects and compared to our SEM data base of thousands of micrographs, and found to be comparable. The current sample consisted of 10 diabetes patients, whose micrographs were also comparable to this database, and also found to be comparable.
Currently a hemochromatosis database is being created. Preparation of blood samples Whole blood samples from healthy individuals, individuals with diabetes and hemochromatosis were obtained in citrated blood tubes.
Final iron concentration is therefore 0. Literature metioned that in iron overload the plasma NTBI levels are 0. Scanning Electron Microscopy SEM procedure Before further processing the samples were incubated at room temperature for 10 minutes.
After incubation the samples were immersed in 0.
The samples were then fixed in a 2. In a typical whole blood smear of healthy individuals, the RBCs are discoid in shape. With the addition of thrombin, fibrin fiber nets form around and over the RBCs.
In general, in healthy individuals the RBCs do not change shape due to the pressure of the fibrin fibers laying over them Figure 1 B.