Anemia ANEMIA • A condition in which the haemoglobin content of blood is lower than normal as a result of a deficiency of one or more essential nutrients, regardless of the cause of such deficiency. Anemia is defined as a reduction of Hemoglobin level in the blood, below the lower extreme of the normal range for the age and sex reduction in oxygen-transporting capacity of blood STRUCTURE OF HEMOGLOBIN • Hemoglobin molcule is a tetramer consisting of two pairs of similar polypeptide chains called globin chains. • To each of the four chains is attached heme which is a complex of iron in ferrous form and protoporphyrin. • The major (96%) type of hemoglobin present in adults is called HbA and it has: Ø 2 alpha globin chains and Ø 2 beta globin chains (a2b2) RBC PRODUCTION In well-nourished persons who become anemic because of acute bleeding or increased red cell destruc7on (hemolysis) the compensatory response can increase the produc7on of red cells five- to eight-fold ADULT REFERENCES RANGES FOR RED BLOOD CELLS DIFFERENT DEGREES OF ANEMIA >10 g /dL (mild) 8-10 g /dL (moderate) < 8 g /dL(severe) SYSTEMS OF CLASSIFICATION 1. Classification of anemia according to underlying mechanism (Blood loss, Impaired RBC production, Excessive RBC distruction) 2. Classification based on red cells morphology (Normochromic, Hypochromic, Normocytic, Microcytic, Macrocytic) CLASSIFICATION OF ANEMIA ACCORDING TO UNDERLYING MECHANISM ANEMIA OF BLOOD LOSS: HEMORRHAGE The anemia is normocytic and normochromic • Acute Blood loss Clinical signs depend on the degree of anemia, the duration (acute or chronic), and the underlying cause. In acute blood loss, the patient usually presents with tachycardia, pale mucous membranes, bounding or weak pulses, and hypotension. • Chronic Blood loss Patient with chronic anemia have had time to adjust, and their clinical presentation is usually more indolent with vague sign of lethargy , weakness, and anorexia. These patients will have similar physical examination findings, pale mucous membranes, tachycardia, and possibly splenomegaly or a new heart murmur, or both. Recovery from blood loss anemia is enhanced by a compensatory rise in the erythropoietin level, which stimulates increased red cell production and reticulocytosis within a period of 5 to 7 days CLASSIFICATION OF ANEMIA ACCORDING TO UNDERLYING MECHANISM CLASSIFICATION OF ANEMIA ACCORDING TO UNDERLYING MECHANISM HEMOLYTIC ANEMIAS • Are associated with erythroid hyperplasia in the marrow. • Increased numbers of reticulocytes in the peripheral blood. • In severe hemolytic anemias, extramedullary hematopoiesis may appear in the liver, spleen, and lymph nodes. HEMOLYTIC ANEMIAS Destruction of red cells can occur within the vascular compartment (intravascular hemolysis): • leads to hemoglobinuria, hemosiderinuria. hemoglobinemia, and • The conversion of heme to bilirubin can result in unconjugated hyperbilirubinemia and jaundice. • Haptoglobin, a circulating protein that binds and clears free hemoglobin, is completely depleted from the plasma. • High levels oflactate dehydrogenase (LDH) as a consequence of its release from hemolyzed red cells. HEMOLYTIC ANEMIAS • Extravascular hemolysis, primarily takes place within the spleen and liver for large numbers of macrophages responsible for the removal of damaged or immunologically targeted red cells. • Because extreme alterations of shape are necessary for red cells to navigate the splenic sinusoids, any reduction in red cell deformability makes this passage difficult and leads to splenic sequestration and phagocytosis. • often produces jaundice and the formation of bilirubin-rich gallstones (pigment stones). Haptoglobin is decreased, and LDH levels also are elevated. • In most forms of chronic extravascular hemolysis there is a reactive hyperplasia of mononuclear phagocytes that results in splenomegaly. SYSTEMS OF CLASSIFICATION 1. Classification of anemia according to underlying mechanism (Blood loss, Impaired RBC production, Excessive RBC distruction) 2. Classification based on red cells morphology (Normochromic, Hypochromic, Normocytic, Microcytic, Macrocytic) CLASSIFICATION BASED ON RED CELLS MORPHOLOGY These features are judged subjectively by visual inspection of peripheral smears and also are expressed quantitatively using the following indices calculated by specialized instruments in clinical laboratories : • Hematocrit test measures the proportion of red blood cells in your blood. • Mean cell volume (MCV): the average volume per red cell. • Mean cell hemoglobin (MCH): the average mass of hemoglobin per red cell. • Mean cell hemoglobin concentration (MCHC): the average. concentration of hemoglobin in a given volume of packed red cells. • Red cell distribution width (RDW): the coefficient of variation of red cell volumen. CLASSIFICATION BASED ON RED CELLS MORPHOLOGY The rise in marrow output is signaled by the appearance of increased numbers of newly formed red cells (reticulocytes) in the peripheral blood. By contrast, anemias caused by decreased red cell production (aregenerative anemias) are associated with subnormal reticulocyte counts (reticulocytopenia). CLASSIFICATION BASED ON RED CELLS MORPHOLOGY MCH: <28 pg Hypochromic > 34 pg Hyperchromic MCV <81 fl >97 fl NORMOCYTIC-NORMOCHROMIC ANEMIA • Is a condition in which the size and Hgb content of RBCs is normal but the number of RBCs is decreased. • It includes: Ø Aplastic anemia due to BM failure Ø Blood loss anemia Ø Hemolytic anemia MICROCYTIC-HYPOCHROMIC ANEMIA • Many RBCs smaller than nucleus of normal lymphocytes • Increased central pallor • Includes: Ø Iron deficiency anemia Ø Thalassemia Ø Anemia of chronic disease Ø Sideroblas6c anemia Ø Lead poisoning MACROCYTIC-NORMOCYTIC ANEMIA MEGALOBLASTIC ANEMIA Ø Vitamin B12 deficiency Ø Folate deficiency Ø Abnormal metabolism of folate and Vitamin B12 NON MEGALOBLASTIC ANEMIA Ø Liver disease Ø Alcoholism Ø Post splenoctomy Ø Neonatal macrocytosis Ø Stress erythropoiesis SIGNS AND SYMPTOMS HB Diminished O2carryng capacity Hypoxia in organs and tissues Signs and Symptoms SIGNS AND SYMPTOMS Depends on: • Degree of anemia • Rapidity of onset (rapid àcardiovascular compensatory reactions VS slowlyàthere is time for compensation, the pt remains asymtomatic) • Age • Comorbidity • Astenia (80%) SYMPTOMS • Difficulty concentrating (70%) • Insomnia (25%) • Depression (20%) • Headache (20%) • Tinnitus, vertigo (15 %) • Shortness of breath particularly with exercise (7%) • Leg cramps In chronic forms serious interference in relationship with severe limitations of daily activity SIGNS • Pale skin and mucous membranes (lips , nail bed , conjunctiva ) ( 80 % ) • Nail dystrophies and fissures ( 40 % ) • Angular cheilitis ( 40 % ) • Hair Loss ( 35 % ) • Glossitis ( 40 % ) • Tachycardia and / or cardiac murmurs ( 50 % ) SIGNS AND SYMPTOMS DIAGNOSIS OF ANEMIA • Patient history • Dietary habits • Medication • Possible exposure to chemical and/or toxins • Description and duration of symptoms • Tiredness • Muscle fatigue and weakness • Headache and vertigo (dizziness) • Dyspnea (difficult or labored breathing) from exertion • GI problems • Signs of blood loss such as hematurie (blood in urine) or black stools DIAGNOSIS OF ANEMIA Physical exam General findings might include: Ø Hepato or splenomegaly Ø Heart abnormalities Ø Skin pallor Specific finding may help to estabilish the underlying cause: Ø In vitamin B12 deficiency there may be signs of malnutrition and neurological changes. Ø In iron deficiency there may be severe pallor, a smooth tongue, and esophageal webs. Ø In hemolytic anemias there may be jaundice due to the increased levels of bilirubin from increased RBC destruction. Thalassemias • Thalassemias are a diverse group of inherited disorders caused by genetic mutations affecting the globin chain component of the hemoglobin (Hb) tetramer. • It is due to decreased production of at least one globin polypeptide chain (beta, alpha, gamma, delta) which results in unbalanced hemoglobinsynthesis. • There are two types of thalassemia: Ø Alpha ThalassemiaàThe alpha thalassemia pa?ent’s does not produce enough alpha protein. This type is commonly found in Souther China, Southest Asia, India, the Middle East, and Africa. Ø Beta Thalassemiaàwe need two globin genes to make beat globin chains. We get one from each pa?ent. If one or two of these genes are faulty, it produces beta thalassemia. THALASSEMIAS: CLASSIFICATION THALASSEMIAS THALASSEMIAS: SIGNS AND SYMPTOMS • The mayority of infants with beta thalassemia will not have symptoms until they reach six months, because they start off with a different type of hemoglobin called fetal hemoglobin. After the age of six months “normal“ hemoglobin starts replacing the fetal one. • People with thalassemia mainly have anemia-like symptoms: Ø Ø Ø Ø Ø Jaundice Fatigue Pale skin Cold hands and feet Shortness of breath THALASSEMIAS: DIAGNOSIS • Most children with moderate to severe thalassemia are diagnosed by the end of their second year. • People with no sympoms may not realize until they have a child with thalassemia and are diagnosed as carriers. • If there is suspects of thalassemia, certain blood tests may be ordered: Ø A complete blood count (CBC) Ø Iron Ø Genetic testing THALASSEMIAS: TREATMENT Blood transfusions This is done to replinish hemoglobin and red blood cell levels. Pa5ents with moderate to severe thalassemia will have repeat trasfusions every 4 months, while those more severe disease may require transfusions every two to four weeks. Pa5ents with mild symptoms may require occasional transfusions when they are ill or have an infec5on. Iron chela;on This involves removing excess iron from bloodstream. Some5mes blood transfusions can cause iron overload. Iron overload is bad for the heart and some other organs. Pa5ents may be prescribed subcutaneous (injected under the skin) deferoxamine or oral (taken by mouth) deferasirox. IRON DEFICIENCY ANEMIA • The most frequent cause of anemia. • Microcytic, Hypochromic, low serum, ferritin and iron levels, low transferrin saturation. • Amount of total iron in the body= 3-5 gms. • Out of this, 50-75%-hemoglobin (1 gm Hb contains 3.34 mg iron). CAUSES OF IRON DEFICIENCY • Reduced intake (very rare in Western countries if not in very deficient and strictly vegetarian diets). • Reduced absorption by gastroresections, enteritis, chronic intestinal diseases, and especially celiac disease. • Increased iron needs during growth, pregnancy and lactation. • Losses (most frequent cause): these are 75% gynecological losses, as they are in pregnancies and in patients with hyperpolimenorrhea. Another cause is intestinal losses. Multiple blood donations also fall into this category. INTESTINAL ABSORPTION OF IRON: • - in the duodenum • - regulation (by the synthesis of apoferritin within mucosal cells). • About 10 % to 15 % comes from meat, fish, and poultry as heme. • About 85 % to 90% comes from grains and vegetables as non-heme iron. 1. The heme iron (unknown mechanism) 2. The nonheme iron •is not readily absorbed (chelates with oxalates, phytates, etc.) •vit. C uptake increases the Iron sources: ü meat, liver, fish, eggs, green vegetables, cereals IRON METABOLISM IRON DEFICIENCY ANEMIA IRON DEFICIENCY ANEMIA: SIGNS AND SYMPTOMS • Most common: pallor • Second most common: inflammation of the tongue (glossitis) • Chelitis: inflammation/fissures of lips • Sensitivity to cold • Weakness and fatigue DIAGNOSIS: • CBC • Iron studies diagnostics • Iron levels: total iron-binding capacity (TIBC), Serum ferritin • Endoscopy/Colonocopy IRON DEFICIENCY ANEMIA: TREATMENT •Oral supplemental iron •Rarely parenteral iron Iron therapy without pursuit of the cause is poor practice; a bleeding site should be sought even in cases of mild anemia. Oral iron Adverse effects include cons=pa=on or other GI upset. Ascorbic acid either as a pill (500 mg) or as orange juice when taken with iron enhances iron absorp=on without increasing gastric distress. Parenteral iron causes a more rapid therapeutic response than oral iron does but can cause adverse effects, most commonly allergic reactions or infusion reactions (eg, fever, arthralgias, myalgias). Parenteral iron is reserved for patients who do not tolerate or who will not take oral iron or for patients who steadily lose large amounts of blood because of capillary or vascular disorders (eg, hereditary hemorrhagic telangiectasia). MEGALOBLASTIC ANEMIAS • Megaloblastic anemia is a general term used to describe a group of anemias caused by impaired DNA synthesis. • The two principal causes of megaloblastic anemia are Vitamin B12 deficiency and folate deficiency . Both vitamins are required for DNA synthesis. • Megaloblasts are characterized by impairement of nuclear maturation and cell division. • Megaloblasts are larger than normal erythroid progenitors (normoblasts) and have delicate, finely reticulated nuclear chromatin (indicative of nuclear immaturity). • apoptosis in the marrow (ineffective hematopoiesis). MEGALOBLASTIC ANEMIAS • Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach • Once ingested Viatmin B12 is bound to R protein in the stomach. • Pancreatic proteases release Vitamin B12 from R proteins in the small intestine, where it binds to intrinsic factor (IF). • Bound to IF, which is produced by gastric parietal cells, Vitamin B12 is trasported to the terminal ileum. • Enterocytes in the terminal ileum absorb Vitamin B12 , break the Vitamin B12 into the portal circulation bound to trascobalamin II. MEGALOBLASTIC ANEMIAS • Vitamin B12 is then trasported to different 2ssues throughout the body. • The primary role of Vitamin B12 is serving as a cofactor for two major metabolic reactions. • Humans recycle Vitamin B12 via the enterohepa2c circula2on; it is excreted in bile and reabsorbed in the terminal ileum. • The liver stores 2 to 3 mg of Vitamin B12. Absorption Of Vitamin B12 MEGALOBLASTIC ANEMIAS MEGALOBLASTIC ANEMIAS • Folate is naturally present in a wide variety of foods, including vegetables (especially dark green leafy vegetables), fruits and fruit juices, nuts, beans, peas, seafood, eggs, dairy products, meat, poultry, and grains. • Normally absorbed both in the small intestine and colon, with a decreasing absorptive gradient from jejunum to colon. • Folate acts as co-enzyme for 2 important biochemical reactions involvinf transfer not 1-carbon units to form other compounds. • These reactions are: 1. Thymidilate Synthetase Reaction 2. Methylation of Homocisteine Methionine to MEGALOBLASTIC ANEMIAS • Folic acid derivates are acceptors and donors of one-carbon units for all axidation levels of carbon. • The active coenzyme form is tetrahydrofolate (THF) • In folate deficency, THF production is depleted causing slowing of DNA synthesis, resulting in pancytopenia due to defective haematopoiesis. • The cells that are produced have immature nuclei compared to the degree of maturation of cytoplasma due to arrest of nuclear maturity. • The biosynthetic pathways of methionine, homocysteine, purines, and thymine rely on one-carbone units being provided by THF. MEGALOBLASTIC ANEMIAS Normal red cells Macrocytic red cells MEGALOBLASTIC ANEMIAS: SYMPTOMS • The most common symptom of megaloblastic anemia is fatigue. • Symptoms can vary from person to person. • Common symptoms include: • • • • • • • • • • • • shortness of breath muscle weakness abnormal paleness of the skin glossitis (swollen tongue) loss of appetite/weight loss GENERAL SYMPTOMS OF diarrhea ANEMIA nausea fast heartbeat smooth or tender tongue tingling in hands and feet numbness in extremities Neurologic symptoms including paresthesia, sensory deficits, hypotonia, seizures, and neuropsychiatric changes MEGALOBLASTIC ANEMIAS: DIAGNOSIS à à à à • Full blood Count (FBC) à • Hb/Hct; MCV, retics, WBC, PLT, macroovalocytosis, anisocytosis, poikilocytosis, hypersegmentation of granulocytes. Also there may be variable thrombocytopenia. • Bone marrow smear: Bone marrow examination reveals myeloid cell changes (giant bands, metamyelocytes and hypertsegmentation) and megakariocytes are decreased and show abnormal morphology. • Serum cobalamin level. • Serum folate level. • Erythrocyte folate level. MEGALOBLASTIC ANEMIAS: TREATMENT • Treated by folate/Cobalamin replacement. • Dietary cobalamin does not correct the anemia. Ø S8ll important to emphasize adequate dietary intake. • Encourage pa8ents to eat foods with large amounts of folic acid. Ø Leafy green vegetables Ø Liver Ø Mushrooms Ø Oatmeal Ø Peanut buEer Ø Red beans CONCLUSIONS • Anemia occurs when a low number of RBCs are circulating in the body. This reduces the person’s oxygen levels and can lead to symptoms such as fatigue, pale skin, chest pain, and breathlessness. • There are over 400 types of anemia. Common causes are blood loss, reduced or impaired RBC production, and the destruction of RBCs. • The most common type is iron-deficiency anemia. It sometimes develops due to a diet lacking in nutrients, Crohn’s disease, or the use of certain medications. • CBC blood test is usually used to detect anemia. Treatment varies, depending on the type, but it may include iron or vitamin supplements, medications, blood transfusions, and bone marrow transplants. • However, for some people with anemia, dietary changes can resolve the issue.
