Anemia Lecture Notes PDF

Anemia  Definition: Reduction in the total number of RBCs, hemoglobin and/or hematocrit below normal for age and sex. Functionally: Impaired oxygen delivery.  Diagnosis of Anemia Hb conc. RBC count. Hematocrit. RBC Indices. Blood smear. HAEMATOCRIT VALUE...

Anemia  Definition: Reduction in the total number of RBCs, hemoglobin and/or hematocrit below normal for age and sex. Functionally: Impaired oxygen delivery.  Diagnosis of Anemia Hb conc. RBC count. Hematocrit. RBC Indices. Blood smear. HAEMATOCRIT VALUE (ratio) (HV) = Packed cell volume (PCV) It is a percentage ratio of red blood cells in blood. i.e. Total ratio of RBCs to total blood volume. Normal H.V values: 47% 42% 40% for for for adult adult children male female The haematocrit value = The packed cell volume PCV. Factors Affecting PCV Laboratory calculation for: 82-96 µm3 27-33 pg 33-37 gm/dL  Morphologic Classification of Anemia Normocytic MCV 86 MCHC 33 Normochromic (Aplastic anemia) Microcytic MCV 96 MCHC < 34.5 Folic acid def. (Megaloblastic anemia) Vitamin B12 def.  Anemia causes Functional Classification: Decreased production Increased destruction 1- Lack of erythropoietin (EPO) 1-Hemorrhage 2- Damage to bone marrow 2-Hemolysis 3-Deficiency of nutrients: Iron Folic acid Vit B-12  Normal shape with decrease in number Destruction of red bone marrow by bacterial toxins, drugs or radiation  Fe Deficiency Anemia Microcytic hypochromic anemia Causes: 1- Poor diet: what are the food sources of Fe. 2- Increased requirements: infants, children, pregnancy. 3- Chronic blood loss: GIT bleeding. 4- Impaired absorption: gastrectomy. Megaloblastic Anemia = Macrocytic Anemia Folic acid def. B12 def. Diet: meat, liver & kidney. Dietary sources: Causes of def: Leafy green vegetables, Vegetarian diet. some fruits & liver. Pernicious Anemia: Autoimmune atrophy of gastric mucosa lack of intrinsic factor inability to absorb vit-B12 macrocytic anemia + neurological lesions.  Increased destruction of RBCs Hemorrhage: Acute blood loss. Hemolysis: Premature lyses of RBC → hemolytic anemia. Infections: malaria Genetic membrane defects Genetic Hb abnormalities: (Sickle cell disease, Thalassemia) ‫انيميا البحر المتوسط نقص ف الجين ال يكون الجلوبين‬ Genetic enzyme defects: Glucose-6-phosphate dehydrogenase (G6PD) ‫انيميا الفول‬  Polycythemia Abnormal increases in the RBC. Increases blood viscosity. Acclimatization to high altitude: The decrease in atmospheric pressure. Decreased O2 partial pressure. Stimulation of erythropoiesis. Increased RBC count → physiological polycythemia.  Platelets (Thrombocytes) Flattened, disk-like cell fragments. Essential for hemostasis. Each platelet circulates for 9-12 days. Removed by splenic macrophages. There are 250.000 – 400.000/ cubic mm. Synthesis: Produced in the bone marrow. Large cells called Megakaryocytes release fragments (platelets) into the circulation. 15  White blood cells (WBC) Classification of WBC WBC are transported by blood from the bone marrow to their major sites of activity. The majority of their functions occur when they leave the blood circulation to enter other body tissues. Granules in the Differential WBC count: cytoplasm Total WBC: 5000 - 11,000/µl Neutrophils: 50 - 70 % Eosinophils: 3- 5 % Basophils: 0.5 % Monocytes: 3 - 8 % Lymphocytes: 20 - 30 % No granules in the cytoplasm Never Let Monkey Eat Banana Leukopoiesis  Neutrophils 50-70% of circulating WBCs. Two type of Granules. Nucleus segmented  polymorphonuclear leukocytes. Functions: Highly mobile and are the first WBCs to arrive at a site of injury. Phagocytic. Lifespan of about 6hrs to a few days. Their % increases in cases of: Acute inflammation e.g: bacterial infections.  Defensive function of neutrophils through the following steps Margination. Neutrophils stick to capillary wall. Diapedesis. Neutrophils squeeze themselves through capillary wall to tissue spaces. Chemotaxis. Chemical attraction of neutrophils by bacterial toxins. Phagocytosis. Neutrophils ingest bacteria by endocytosis &fuse with lysosomes to kill bacteria.  3-5% of circulating WBC. EOSINOPHILS Reddish-orange staining granules. Bi-lobed nucleus. Functions: Phagocytose antibody-coated bacteria& protozoa. Exocytose toxic compounds onto the surface of large multi-cellular parasites such as parasitic worms. Typical lifespan 8-12 days. Their % increase in: parasitic infections. Allergic reactions (asthma, fever).  BASOPHILS Less than 1% of WBC Have large deep blue cytoplasmic granules which cover the nucleus. Functions: Migrate to injury sites and discharge the contents of their granules. Histamine Vasodilator and increaser of capillary permeability. Heparin: anticoagulant.  MONOCYTES 3- 8 % of WBC in blood. Their nuclei deeply indented, kidney-shaped. Functions: Have more phagocytic power than neutrophils & longer life span. Leave the bloodstream to become tissue macrophages.  LYMPHOCYTES 20-30% of circulating WBC. Large nucleus & thin halo of cytoplasm. Life span of hr to years. Non- phagocytic cells. Types: 1) T- Lymphocytes: Defend against foreign cells and tissues and coordinate the immune response (Cell mediated immunity). 2) B- Lymphocytes: Produce and distribute antibodies - proteins that attack foreign molecules (Humoral immunity).  Leukemia Uncontrolled production of large number of immature of leucocytes which are non-functional. Causes: Malignant disease of the bone marrow, extreme leukocytosis and inflammation. Leukopenia An inadequate number of WBCs (< 4,000 /µl). Causes: Viral infections, sever bacterial infections and bone marrow disorders.  Hemostasis Definition: stoppage of blood loss from injured vessel. Phases: 1. Vascular Phase. 2. Platelet Phase. 3. Coagulation Phase. 4. Fibrinolysis. and resolution phase. 2  1-Vascular Phase The smooth muscle cells in the blood vessel wall respond to damage by contraction. the blood vessel diameter decreases lead to reduction in blood loss. Vasoconstriction (VC) is due to: 1) Sympathetic reflex in response to pain. 2) Local myogenic vasospasm in response to injury. 3) Locally produced VC released from damaged tissues and platelets. 3  2-Platelet plug Platelet Phase: Platelets attach to the sticky & rough surface in presence of Von Willebrand factor (protein). Platelets activate release chemicals (thromboxane A2) that attract and activate more platelets. A mass of platelets temporarily plugs the damage. 5 Platelet function: platelet plug 7  3-Coagulation Phase A sequence of chemical reactions convert fibrinogen (soluble circulating plasma protein) into a meshwork of the insoluble protein fibrin. The fibrin meshwork grows & cover the surface of the platelet plug. More RBC & platelets are trapped to form a blood clot. During the coagulation phase enzymes and proenzymes interact. The activation of one proenzyme creates an active enzyme that activates another proenzyme that will then activate a third and so on yielding a chain reaction. 8  Extrinsic Pathway Begins with the release of tissue factor by damaged endothelial cells or peripheral tissues. The greater damage the more tissue factor released, and the faster clotting will occur. In a few short steps, a chemical called prothrombin activator will have been formed. Because only a few steps are required, the extrinsic path forms prothrombin activator quickly. 11  Intrinsic Pathway Begins with the exposure of collagen which starts the activation cascade of several proenzymes eventually resulting in the production of prothrombin activator. Because there are several steps, the intrinsic path does not make prothrombin activator as fast as the extrinsic path. However, multiple steps allows for more amplification which means more prothrombin activator will be made. 12 12 11 7 9 8 10 10 5-Fibrinolysis 4-Clot retraction Platelet’s actin and myosin fibrils, contract clot retraction Firm & stable clot. This also reduces the size of the injured area, making it easier for fibroblasts, smooth muscle cells and endothelial cells to complete repairs. 5-Fibrinolysis As repairs proceeds, the clot gradually dissolves fibrinolysis. It begins with the activation of the proenzyme plasminogen into plasmin that digests the 13 fibrin strands and erodes the foundation of the clot.  Endogenous Inhibitors of Hemostasis Anticlotting system The normal endothelium: intact & smooth. Heparin which inhibits thrombin formation. Endothelium also secretes products which inhibit platelets: Prostacyclin which inhibits platelet aggregation. Protein C which inhibit factors V, VIII. Antithrombin(AT) (also called antithrombin III from the liver, inhibits thrombin (factor II). Thrombomodulin which binds thrombin (anticoagulant). Heparin from mast cells enhances AT. 15  Bleeding Disorders Platelet disorders: Thrombocytopenia plat 50.000. purpura. Blood vessel wall disorders. Congenital Coagulopathies: Hemophilia A: def. of Factor VIII. Hemophilia B: def. of Factor IX. Von Willibrand’s diseases. Acquired Coagulopathies: Vitamin K Def, (VII,IX,X ) Liver Diseases: Hypoprothrombinemia. 16  Vitamin K def: Synthesized by bacterial flora in large intestine. Stimulates liver synthesis of factors II, VII , IX , X. Deficiency in: Newborns especially premature ones. Prolonged use of antibiotics. Obstructive jaundice &chronic diarrhea. 17  Thrombosis ‫الجلطة‬ Formed when platelets stick to the wall of an intact blood vessel. This occurs in areas where endothelial cells of vessel walls contain lots of lipid's plaques. A large thrombus may block a vein (Deep Vein Thrombosis DVT). Blood stasis increase risk of DVT. Causes: Immobilization after fractures/ surgery. Long flights. Exogenous anticoagulants: Heparin: works by inactivating thrombin. Coumarin, Warfarin: prevents the liver from utilizing vitamin K (necessary for the production of clotting factors). Aspirin: inhibits platelet aggregation. 18  The ABO blood groups The ABO blood groups are defined by specific inherited antigens, that are present on the surface of red blood cells. An individual does not contain antibodies to the antigens on their red blood cells. i.e. A person with an A antigen would not have an A antibody but antibody to antigens that are not present (anti-B). Blood Types Prevalence of different groups  Rh- blood groups Based on presence (Rh+) or absence (Rh-) of one of Rh antigens. Named for Rhesus monkey. Most people are Rh+. Rh- person will develop an immune response to Rh+ blood. A person with Rh- blood doesn’t have Rh antibodies. Naturally in the plasma. A person with Rh- blood can develop Rh antibodies in the plasma if he or she receives blood from a person with Rh+ blood.  Mother-fetus incompatibility (Hemolytic Disease of the Newborn HDN) 28  Prevention of HDN: Administer anti-D (Rh) immunoglobulin to the mother within 72 hours after delivery. This will destroy any fetus cells in mother circulation and stops any immunological reaction. Erythroblastosis Fetalis HDN: RBCs of newborn are destroyed in a maternal immune reaction resulting from a blood group incompatibility between the fetus and its mother. Anemia. Anemia + jaundice sever cases death in utero 29 (Erythroblastosis fetalis).  Blood Groups and transfusions Large losses of blood have serious consequences. Loss of 15 to 30 % causes weakness. Loss of over 30 % causes shock, which can be fatal. Transfusions are the only way to replace blood quickly. Transfusions Consider recipient (plasma Vs. donor cells). Universal donor (has no antigens) O Universal recipient (has no antibodies) AB 31  Transfusion Indications Acute blood loss. Anemia or chronic blood loss. Deficiency of clotting factors. Fresh frozen plasma or cryoprecipitate. Miss-match reactions If group A red cells are mistakenly transfused to a group O/B recipient, the anti-A antibody in the recipient’s plasma destroys the transfused group A cells and a serious transfusion reaction occurs.