Week 2 Anemia F24 Student Slides PDF

PATH 1017 Anemia Professor Jennifer Lamarre PATH 1017 2024-2025 1 Anemia Abnormally low level of: Hemoglobin Circulating RBCs Or both Leads to: Decreased oxygen carrying capacity of blood PATH 1017 2024-2025 2 Anemia can res...

PATH 1017 Anemia Professor Jennifer Lamarre PATH 1017 2024-2025 1 Anemia Abnormally low level of: Hemoglobin Circulating RBCs Or both Leads to: Decreased oxygen carrying capacity of blood PATH 1017 2024-2025 2 Anemia can result from… Impaired Increased Massive or production of destruction of chronic blood RBCs RBCs loss Nutritional Hemolytic Trauma deficiencies Sickle cell GI bleed Aplastic Thalassemia PATH 1017 2024-2025 3 General manifestations are caused by: 1. ↓hemoglobin List the common manifestations related to each: 2. Hypoxia from deficient O2 transport 3. Compensatory mechanisms attempting to increase O2 delivery PATH 1017 2024-2025 4 Diagnostic Tests Complete Blood Count (CBC) Hemoglobin [Hgb] Hematocrit (Hct) RBC count RBC size (MCV) & RBC colour (MCHC) indices are used to differentiate anemia types Blood Smear Stained smear of blood viewed under microscope Bone Marrow Aspiration If blood smear abnormal Sites: posterior Iliac crest or sternum PATH 1017 2024-2025 5 CBC –> MCV and MCHC MCHC (mean MCV (mean corpuscular corpuscular hemoglobin volume) concentration) ↓ MVC= microcytic ↓ MCHC/colour = (small cell) anemia hypochromic ↑ MCV=macrocytic ↑ MCHC/colour= (large cell) anemia hyperchromic Normal MCV= Normal MCHC/colour= Normocytic anemia normochromic PATH 1017 2024-2025 6 Additional diagnostic tests for specific anemias Iron level: Ferritin, Total iron-binding capacity (TIBC) Serum B12 level Gastric acid levels Antibodies to intrinsic factor Schilling test (B12 excretion) PATH 1017 2024-2025 7 Anemias of Deficient RBC Production Iron deficiency Often caused by blood loss anemia Dietary deficiency Vitamin B12-deficiency (pernicious Megaloblastic anemia) anemias Impaired DNA synthesis = enlarged red cells Aplastic anemia Bone marrow depression Chronic inflammation Chronic disease Chronic renal failure anemias Chronic infections PATH 1017 2024-2025 8 Iron-Deficiency Anemia Decreased iron present required for hemoglobin synthesis. Decreased oxygen carrying capacity What lab results are RBCs are: expected? Hypochromic & microcytic Poikilocytosis (irregular shape) Anisocytosis (irregular size) PATH 1017 2024-2025 9 Iron-Deficiency Anemia Etiology: What are some possible Chronic blood loss, causes in: Deficient diet Women? Increased demands Adolescents? Treatment: Improved diet Children? Iron supplements Identification of cause Medication-related? of blood loss PATH 1017 2024-2025 10 Iron-Deficiency Anemia Symptoms Fatigue Chronic State Lethargy Tachycardia SOB Weakness Hypotension Pallor Brittle nails Cold intolerance Spoon-shaped fingernails Loss of concentration Stomatitis Irritability Glossitis Loss of appetite Fissures in corners of mouth Pica PATH 1017 2024-2025 11  Vitamin B12 Deficiency Anemia Megaloblastic anemia Erythrocytes are large(macrocytic), often with oval shape Poikilocytosis and teardrop shapes Why is vitamin B12 necessary for RBCs? How does lack of B12 affect RBCs? What lab results are expected? PATH 1017 2024-2025 12  B12-deficiency anemia Etiology: Vitamin B12 deficiency Pernicious anemia (from atrophic gastritis) lack of intrinsic factor in the stomach (antibodies often present) Treatment: Vitamin B12 injections regularly Prognosis: Good with treatment PATH 1017 2024-2025 13 Manifestations:B12-deficiency anemia Classic symptoms of anemia Nervous system problems – Why? Numbness, tingling and burning in feet and hands Mental impairment, delusions, irritability Depression PATH 1017 2024-2025 14 Aplastic Anemia RBC normal in size and shape but not enough of them because of failure of the red bone marrow Bone marrow is fatty and unable to produce RBC PATH 1017 2024-2025 15 Aplastic Anemia Etiology congenital, industrial chemicals (benzenes, insecticides), infections, chemotherapy drugs, idiopathic (in 2/3 cases) Pathophysiology exposure → depression of bone marrow → decreased production of RBCs, WBCs, and platelets Manifestations Onset is insidious fatigue, weakness, pallor, petechiae and ecchymosis, bleeding , increased risk of infection etc. PATH 1017 2024-2025 16  Aplastic anemia Diagnosis Treatment: Prognosis: CBC – what correction of Poor if no results are underlying treatment expected? cause 70% survive RBC with BMT transfusions, Immuno- Bone marrow medications suppressive biopsy such as therapy- 50% erythropoietin and corticosteroids bone marrow transplant PATH 1017 2024-2025 17 Hemolytic Anemia Excessive hemolysis or destruction of abnormal RBC Etiology: fragile or abnormal RBC are destroyed by the liver, spleen and bone marrow. Pathophysiology Hemolysis of RBC produce excess amounts of byproducts – iron, bilirubin Decreased circulating mature RBC, decreased oxygen carrying capacity Increased clumping of RBC – embolisms/clots form PATH 1017 2024-2025 18 Manifestations Mild: classic anemia Can you explain why symptoms these manifestations occur? Severe: Jaundice, hemoglobinuria, hemoglobinemia, hypotension, dyspnea, splenomegaly, back and joint pain PATH 1017 2024-2025 19 Hemolytic anemia Dx and Tx Additional diagnostic tests: LDH (lactic dehydrogenase)– released when tissue is damaged. Coomb’s test (antiglobulin test) detects antibody on RBC that indicates immune system cause Treatment: determined by cause PATH 1017 2024-2025 20 Sickle Cell Disease Recessive inheritance Mutation in beta chains of hemoglobin (HbS) When hemoglobin is deoxygenated, beta chains link together, forming long protein rods that make the cell “sickle” PATH 1017 2024-2025 21 Sickle Cell Disease- Recessive Inheritance How many mutated genes need to be inherited to have: Full sickle cell disease Sickle cell carrier (Trait) If you carry the trait, will you have symptoms? PATH 1017 2024-2025 22  Pathophysiology Abnormal HbS Mutation on β chain Amino acid substitution When deoxygenated, HbS polymerizes HbS becomes irreversibly sickled Figure 23-8 p574 PATH 1017 2024-2025 23 Consequences of RBC sickling Vessel occlusion Chronic hemolytic anemia Tissue ischemia Sickled cells more likely Acute pain to be destroyed Infarctions cause chronic Jaundice damage to liver, spleen, heart, kidneys, eyes, bones Pulmonary infarction  acute chest syndrome Cerebral infarction  stroke PATH 1017 2024-2025 24 Diagnosis Screening programs Heel stick samples sent for electrophoresis to separate the HbS from HbF and HbA Neonatal Dx Clinical findings Hemoglobin electrophoresis Prenatal Dx Amniocentesis PATH 1017 2024-2025 25 Sickle Cell Anemia Treatment No cure What are some triggers Avoid sickling triggers that are associated with Treatment to reduce sickling and vessel symptoms: occlusion? Pain control Hydration etc. Transfusion may be needed Antibiotics Why blood transfusions? Immunization Hydroxyurea may be used Why antibiotics and to prevent complications immunizations? and reduce pain crises PATH 1017 2024-2025 26 Thalassemias Group of inherited disorders of hemoglobin synthesis Caused by absent or defective synthesis of α or β chains of adult hemoglobin and affects cell maturation Develop hypochromic, microcytic anemia Decrease in Hgb and therefore RBC production RBC are abnormal in shape and short lived. Excessive hemolysis due to odd shape PATH 1017 2024-2025 27 Thalassemias Minor (trait carrier, mild anemia) or Major (full disease) Population affected: Alpha Beta Alpha & Beta Asians Mediterranean Africans population African (Italy and Americans Greece) PATH 1017 2024-2025 28 Thalassemias - pathogenesis Beta chains are defective and fewer produced Alpha chains unaffected and produced as usual. Leads to an imbalance (excess alpha, too β- little beta) thalassemia Excess alpha chains form Heinz bodies which affects ability to mature, cell membranes are weak Leads to excessive hemolysis/destruction Ineffective hematopoiesis and hemolysis => ↑ erythropoietin => ↑ marrow mass PATH 1017 2024-2025 29 Thalassemias - pathogenesis Gene deletion => results in defective α α- chain synthesis thalassemia 3-4 genes deleted causes unstable chains PATH 1017 2024-2025 30  Manifestations of β-thalassemia Usual signs of anemia as well as: Bone deformities –why? Splenomegaly and hepatomegaly- why? Excessively high iron level- why? Hgb levels can be very low, blood and tissue oxygen levels cause multiple problems Increased thrombotic events (stroke etc) PATH 1017 2024-2025 31 Dx and Tx for β-thalassemia Diagnostic tests: Microscopic exam of RBC – microcytic, hypochromic Increased levels of erythropoietin Excessively high iron levels Treatment Bone marrow and stem cell transplantation, experimental gene manipulation are being explored Splenectomy – how might this help? Iron chelation therapy –purpose? If severe, the client will be transfusion dependent starting from 6-9mths of age….Needed Q 3-4wks PATH 1017 2024-2025 32