Hematopathology.pdf

HEMATOPAHOLOGY Diseases of Red Blood Cells Karen Gil MD, MHSN Blood Composition Blood Composition Old red blood cells dye, and part of the heme is eliminated in the feces, other are reused Red Blood Cell cycle Reticulocytes are precursors of Erythrocytes Senescent RBC’s are destroyed by macrophages...

HEMATOPAHOLOGY Diseases of Red Blood Cells Karen Gil MD, MHSN Blood Composition Blood Composition Old red blood cells dye, and part of the heme is eliminated in the feces, other are reused Red Blood Cell cycle Reticulocytes are precursors of Erythrocytes Senescent RBC’s are destroyed by macrophages of the Reticuloendothelial system (RES) in the spleen and liver RBC life span 120 days Erythropoietin and Iron During hypoxia, the kidneys produce erythropoietin (erythropoiesisstimulating hormone) stimulates production of erythroblasts from bone marrow bone marrow can increase the rate of RBC formation by approximately 10 times—about 30 million cells per second This process aids the patient during recovery from a severe loss of blood Hemoglobin synthesis requires iron, available in the diet Hemoglobin contains approximately 65% of the body’s supply of iron, which is about 4,000 mg Red Blood Cells Disorders underproduction (anemia) over production (polycythemia) Diagnosis RBC indices - CBC Microscopic examination of cellular morphologyBlood smear Adult Reference Ranges for Red Blood Cells* Measurement (units) Men Women 13.6-17.2 12.0-15.0 Hematocrit (%) 39-49 33-43 Red cell count (106/μL) 4.3-5.9 3.5-5.0 Hemoglobin (gm/dL) Reticulocyte count (%) 0.5-1.5 Mean cell volume (μm3) 82-96 Mean corpuscular hemoglobin (pg) 27-33 Mean corpuscular hemoglobin concentration (gm/dL) RBC distribution width Hemoglobin normal ranges children: 11.0 to 16.0 g/dl 33-37 11.5-14.5 Anemia Physiologically Impaired oxygen delivery to the tissues due to a reduction in the proportion of Red blood cells Anemias Reduction in the oxygen transport capacity of blood Usually as a result, of a reduction below normal limits of the total circulating red cell mass Resulting in abnormal Hemoglobin levels Hematocrit levels Anemias Classification Classification Blood loss (hemorrhagic anemias) Increased rate of destruction (hemolytic anemias) Inherited: defects within red cells Sickle cell Thalassemia Acquired: toxins (lead, copper, snake or spider venom) drugs (quinin, penicillin allergy) autoimmune diseases, infection (malaria) Insufficient red cell production Deficiency iron, vitamin B12/intrinsic factor, vitamin C, folic acid Kidney failure = lower EPO Destruction of bone marrow tissue (mutations, autoimmune disease, chemicals, drugs, radiation) Reduced erythropoiesis =hypoplastic anemia No erythropoiesis = aplastic anemia Anemia Common disease – 1/3 of the global population Could be mild (asymptomatic) or severe More common in elderly Symptoms: Signs: Weakness Skin cold at touch Malaise (tiredness) Tachypnea Lethargy Hypotension Restless legs Pallor conjunctiva Shortness of breath Jaundice – hemoglobinopathies Chest pain Tachycardia Exercise intolerance Koilonychia (spooning of the nails) Pica (diet deficiency) – iron deficiency Organ failure Anemia Classification Anemias are further divided by the mean corpuscular volume into microcytic anemia (MCV100 fl). MCV Microcytic Normocytic Macrocytic MCV100 fl Iron Deficiency 50% Hemolytic Anemia Vitamin B12 deficiency Thalassemia Aplastic Anemia Folate deficiency Sickle Cell anemia Alcohol abuse Anemia of Blood loss Acute Blood loss: Trauma Surgery Could lead to shock or death After stabilizing, bone marrow compensates increasing reticulocytes Chronic Blood loss: GI –peptic ulcer disease, intestinal polyps, colon cancer GU- uterine diseases (myomas, prolonged menstrual cycles or excessive menstrual cycles) Iron reserves could be depleted, giving rise to iron deficiency anemia Bone marrow activates erythropoiesis an iron becomes available Hemolytic anemia Hemolytic anemia is a disorder in which red blood cells are destroyed faster than they can be made The destruction of red blood cells is called hemolysis Characteristics: Increased rate of RBC’s destruction Accumulation of products of hemoglobin catabolism – Bilirubin Increase bone marrow erythropoiesis – associated to reticulocytosis Hemolytic anemia Intravascular hemoglobinuria hemoglobinemia hemosiderinuria (hemosiderin accumulation due to excess of iron) Extravascular Most common mode of RBC’s destruction NO hemoglobinemia or hemoglobinuria Hemolitic Anemias Hereditary Spherocytosis Sickle Cell anemia Thalassemia Hereditary Spherocytosis Autosomal Dominant disorder Abnormality in the cell membrane skeleton – malleability Conversion of red cells to spherocytes Phagocytosed and removed in the spleen Clinical manifestations Anemia Splenomegaly Sickle Cell Anemia Autosomal recessive disorder Mutation in β-globin that causes deoxygenated hemoglobin to distort shape –sickle or crescent shape Blockage of vessels by sickled cells causes pain crises and tissue infarction Particularly in bone marrow and spleen Blocking of the arterioles can cause organ failure Red cell membrane damage by sickling results in severe hemolytic anemia Can cause proliferative retinopathy due to the crescent or sickle shaped cells occluding retinal vessels Proliferative Sickle Retinopathy Figure 3. Proliferative sickle retinopathy stage 3 with auto-infarction of sea fans in a 21-year-old man with SC Disease. (This image was taken with a fundus camera and was originally published in the ASRS Retina Image Bank by Alan D. Letson, MD, OSU Eye and Ear Institute, Photographer: Beverly Radcliffe. Proliferative Sickle Retinopathy Stage 3. 2012; Image Number, 1224. © the American Society of Retina Specialists). Figure 2. Sea fan formation with neovascularization. Fluorescein angiogram image of an individual with sickle cell retinopathy showing sea fan formation with neovascularization. This image was taken using an Optos P200MA ultra-wide field imaging device. (This image was originally published in the ASRS Retina Image Bank by Michael P. Kelly, FOPS Director, Duke Eye Center Labs, Duke University Hospital, Sickle Cell Retinopathy. 2012; Image Number, 721. © the American Society of Retina Specialists). Sickle cells occlude retinal arterioles, leading to ischemia and subsequent retinal neovascularization “Sea fan” retinopathy due to their characteristic shape Hemoglobin S disease AA substitution in Beta chain - Glutamic acid is substitute by Valine Sickle Cell Anemia Sickle Cell Anemia 1 of 400 African Americans are affect 8% of the African American population are carriers Tx – pain episodes with antiinflammatory agents Hidroxyurea is an antimetabolite use in some cancers – prevent formation of sickle cells Definitive treatment – bone marrow transplant Thalassemias Autosomal dominant disorder Caused by mutation in α or β-globin that reduce hemoglobin synthesis Microcytic hypochromic anemia β-thalassemia unpaired α-globin chins form aggregates that damage red cell precursors and further impair erythropoiesis Mutation common in Mediterranean, African and Asian population General symptoms of hemolytic anemia: fatigue, hepatosplenomegaly, jaundice Thalassemia clinic and genetic classification Pathogenesis of β-thalassemia major Blood transfusion is the main treatment but cause iron overload ineffective erythropoiesis causes a bone marrow expansion Beta-Thalassemia major Chipmunk facies: bone marrow expansion in facial bones will lead to a characteristic physical appearance of a “chipmunk face” Head x-ray sign - Crew haircut Treatment of choice: BONE MARROW TRANSPLANT Bone marrow biopsy Hypocellular bone marrow Normo cellular bone marrow Iron deficiency anemia Most common form of nutritional deficiency anemia Low dietary intake Malabsorption (celiac disease) Increase demands (pregnancy) Chronic blood loss Iron deficiency impairs cellular functions and cause: brittle hair nail spooning pica (eating dirt or ice) microcytic and hypochromic red cells on the peripheral smear Anemia of chronic disease Tuberculosis Parasites Osteomyelitis Chronic infections Chronic immune disorders – Rheumatoid Arthritis Neoplasms Hodgkin lymphoma Carcinomas lung and breast As in Iron deficiency anemias, iron levels are low Red cell will be hypochromic and microcytic Treatment: iron and erythropoietin Treat the cause Megaloblastic anemias Disorders of RBC maturation Two principal causes: Vitamin B12 deficiency Folic acid deficiency Diagnose: measure of Vit B12 and Folic acid in blood Treat the cause macrocytosis Megaloblastic anemia Vitamin B12 deficiency Inadequate intake or malabsorption of vitamin B12 Pernicious anemia most common cause of malabsorption, is an autoimmune condition causing lack of intrinsic factor glycoprotein produced by the parietal cells in the gastric body and fundus plays a crucial role in the transportation and absorption of the vital micronutrient vitamin B12 Vitamin B12 – IM Also available PO and SL (no effective) Megaloblastic anemia Folic Acid deficiency Dietary deficiency is the leading cause and is especially common in alcoholics May also be drug-induced (chemotherapy or methotrexate) Other malabsorption gastrointestinal syndromes Folic Acid deficiency in pregnancy increase the risk of neural tube defect – spina bifida Neoplasm that produce Metastatic lesions in bone tissue produce anemias Breast Prostate Thyroid Multiple Myeloma Lymphomas Leukemias Polycythemia Excess of red cell production Primary – Polycythemia vera is a type of cancer with overproduction of red blood cells Secondary – chronic low oxygen state causes overproduction of EPO, with this a consequent overproduction of red blood cells Causes: Smoking Air pollution Emphysema Living in high altitudes Physical strenuous conditions (athletes) Excess red blood cells cause Increase blood volume Increase blood pressure Increase viscosity Blood clot formation Heart attack Stroke Pulmonary embolism Heart failure Polycythemia Erythema and swelling CRA Occlusion Retinal vascular occlusions Polycythemia Hydroxyurea