Red Blood Cells Associated Disorder: Anemia: Assessment, Analysis, and Associated Dental Management Guidelines
NORMAL IRON METABOLISM
Prior to discussing the different types of anemias, it is important to understand normal iron metabolism. Iron is mainly absorbed in the duodenum and upper jejunum into the intestinal epithelial cells. Iron from within the enterocyte is released into the bloodstream via ferroportin. Iron is then bound in the bloodstream by the transport glycoprotein, transferrin.
Normally, about 20–45% of transferrin binding sites are filled and this is the percent saturation. About 0.1% of total body iron is circulating in bound form to transferrin. Most absorbed iron is utilized in the bone marrow for erythropoiesis. About 10–20% of absorbed iron goes into a storage pool in cells, particularly macrophages.
Iron absorption is regulated by:
- Dietary regulation: When the intestinal mucosal cells have accumulated enough iron, they “block” any additional uptake.
- Stores regulation: As iron stores increase in the liver, the hepatic peptide hepcidin is released. Hepcidin diminishes intestinal mucosal iron ferroportin release. The enterocytes retain any absorbed iron and are sloughed off in a few days. As body iron stores fall, hepcidin decreases and the intestinal mucosa is signaled to release their absorbed iron into circulation.
The composition of the diet may also influence iron absorption. Citrate and ascorbate (in citrus fruits, for example) can form complexes with iron that increase absorption, while tannates in tea can decrease absorption. The iron in heme found in meat is more readily absorbed than inorganic iron by an unknown mechanism. Non-heme dietary iron can be found in two forms: most is in the ferric form (Fe3+) that must be reduced to the ferrous form (Fe2+) before it is absorbed. Duodenal microvilli contain ferric reductase to promote absorption of ferrous iron.
Only a small fraction of the body’s iron is gained or lost each day. Most of the iron in the body is recycled when old RBCs are removed from the circulation and destroyed, with their iron scavenged by macrophages in the mononuclear phagocyte system, mainly the spleen, and returned to the storage pool for re-use. Iron homeostasis is closely regulated via intestinal absorption. Increased absorption is signaled via decreased hepcidin by decreasing iron stores, hypoxia, inflammation, and erythropoietic activity.
Iron is stored in the body in two forms:
Iron is initially stored as a protein-iron complex ferritin, but ferritin can be incorporated by phagolysosomes to form hemosiderin granules. Iron is found in red blood cells as heme in hemoglobin and as storage iron occurring mainly in bone marrow, spleen, and liver, with the remainder in myoglobin and in enzymes that require iron.
Laboratory testing for iron may include tests for:
- Serum iron
- Serum iron binding capacity
- Serum ferritin
- Complete blood count (CBC)
- Bone marrow biopsy
- Liver biopsy
The simplest tests that indirectly give an idea of the iron stores are the serum iron and the iron binding capacity, with calculation of the percent transferrin saturation. The serum ferritin correlates well with iron stores, but it can also be elevated with liver disease, inflammatory conditions, and malignant neoplasms.
The CBC also gives an indirect measure of iron stores, because the mean corpuscular volume (MCV) can be decreased with iron deficiency. The amount of storage iron for erythropoiesis can be quantified by performing an iron stain on a bone marrow biopsy. Excessive iron stores can be determined by bone marrow and by liver biopsies.
ANEMIA FACTS AND CLASSIFICATION
Anemia is a clinical condition associated with a reduction of the RBCs and/or the hemoglobin in the blood. Hemoglobin consists of two protein molecules, heme and globin. Oxygen binds to heme, thus enabling hemoglobin to transport oxygen to the tissues. Anemia is associated with a reduction in the oxygen-carrying capacity of the blood, resulting in tissue hypoxia. This lack of tissue oxygenation accounts for the poor wound healing in anemic patients. Anemia can occur when RBC production is affected. It can also occur with excessive RBC destruction associated with the hemolytic anemias, and excessive RBC loss associated with acute or chronic bleeding. A thorough medical history and physical examination will help assess the type and severity of anemia. The patient’s dietary history, over-the-counter (OTC) and prescribed medications history, ethnicity, and family history will provide additional clues.
The CBC is the basic test used to evaluate anemia. The CBC analyzes various characteristics of the RBCs along with the WBC count, the WBC differential count, and the platelet count.
ANEMIA CLASSIFICATION BY ETIOLOGICAL FACTORS
Sickle-cell anemia is associated with sickle-shaped RBCs.
Major or minor thalassemia is associated with microcytic hypochromic RBCs.
Glucose-6-Phosphate Dehydrogenase (G6PD)–Deficiency Anemia
The MCV and MCHC are normal, and the reticulocyte count is increased.
Hereditary spherocytosis is associated with large spherical RBCs. The MCV and MCHC are normal, and the reticulocyte count is increased.
Iron (Fe) Deficiency
Iron deficiency anemia is associated with a hypochromic, microcytic RBC pattern.
Folic Acid Deficiency
Folic acid deficiency anemia is associated with a macrocytic, normochromic pattern.
Vitamin B12 Deficiency
Vitamin B12 deficiency anemia is also associated with a macrocytic, normochromic RBC pattern.
Celiac or Crohn’s Disease
Celiac or Crohn’s disease is associated with nutritional malabsorption of iron, folic acid, or vitamin B12, resulting in iron, folic acid, or vitamin B12 anemias.
Acquired Iron Deficiency Anemia
Acquired iron deficiency anemia is due to chronic use of aspirin, NSAIDS, or corticosteroids. Chronic use of these drugs can cause gastric mucosal irritation, ulceration, and bleeding. A microcytic, hypochromic RBC pattern is seen on the CBC.
Anemia of Chronic Disease/Malignancy-Related/Early Iron Deficiency/Acute Blood Loss/Chronic Renal Failure
This is the most common anemia in hospitalized persons. It is a condition in which there is impaired utilization of iron, without either a deficiency or an excess of iron. The probable defect is a cytokine-mediated blockage in transfer of iron from the storage pool to the erythroid precursors in the bone marrow. The defect is either inability to free the iron from macrophages or to load it onto transferrin. Inflammatory cytokines also depress erythropoiesis, either from action on erythroid precursors or from erythropoietin levels proportionately too low for the degree of anemia.
Causes of Anemia of Chronic Disease
Causes of anemia of chronic disease can include chronic infections, ongoing inflammatory conditions, autoimmune diseases, and neoplasms. Anemia of chronic disease is addressed by treating the underlying condition.
Anemia of chronic disease is characterized by:
- Normochromic, normocytic RBC pattern is seen on the CBC. The reticulocyte count is decreased. Chronic renal failure (CRF) is associated with low levels of the erythropoietin hormone. Erythropoietin formed in the kidneys is needed for RBC production.
- Total serum iron is decreased.
- Iron-binding capacity is reduced as well, resulting in a normal-to-decreased saturation.
Bone Marrow Infiltration–Associated Anemia
Cancer cell infiltration of the bone marrow (BM) can cause a reduction in any or all of the cell lines: WBC, RBC, and/or platelets. When all cell lines are decreased, the patient is said to have pancytopenia, a status of significant concern in the medical and dental setting. During pancytopenia, the low WBC count can increase the patient’s susceptibility to infection. The low RBC count can cause tissue hypoxia and poor wound healing. The low platelet count can be associated with an immediate type of bleeding and excessive oozing at the time of surgery if the platelet count is significantly decreased.
The congenital types of anemias are associated with alteration in the alpha (α) or beta (β) chains of hemoglobin, or both. The congenital types of anemias occur commonly in the African-American, Middle Eastern, and Mediterranean populations. The anemias appear early on in life. There is often a history of “crisis bouts” starting from childhood that occur through the years. As and when the patient gets exposed to factors that trigger hemolysis, the symptoms and signs of the crisis bouts occur. The patient experiences fever, pain in the long bones, malaise, and worsening of the anemia. Vascular infarction in the long bones causes the bone pains. This classic presentation pattern is most commonly seen with sickle-cell anemia. The spleen is a common site for sequestration of the abnormal red blood cells. With time, this causes the spleen to increase in size. The enlarged spleen causes pain in the upper-left abdominal quadrant, and an enlarged spleen is often the reason for removal of the organ, in severe cases.
Complications Associated with Frequent Hemolysis
Frequent hemolysis increases the incidence of gallstones. Increased RBC breakdown can also increase the serum bilirubin level and the patient can appear jaundiced. Frequent crisis bouts can also cause renal damage. Always check the serum creatinine level prior to dentistry in the hemolytic anemia patients. The hemolytic anemia patient is treated with repeat blood transfusions and, in rare circumstances, by bone marrow transplant.
Sickle-cell patients have a variant of hemoglobin A called hemoglobin S. The S denotes sickle. Hemoglobin S and hemoglobin C are abnormal types of hemoglobin. Sickle-cell disease can present as sickle-cell anemia (SS) or sickle-hemoglobin C disease (SC). Sickle-hemoglobin C disease (SC) is the milder form.
Red blood cells that contain mostly hemoglobin S have a very short life span of about 20 days. The abnormal hemoglobin causes the RBC to become sickle-shaped, and the sickling is exacerbated during the crisis bouts. Sickle cells have difficulty flowing through the lumen of small blood vessels, thus causing obstruction to the flow of blood and resulti/>