Blood Disorders 3 PDF

BLOOD DISORDERS 3 Inadequate dietary supply of nutrients Bone marrow failure (aplastic anemia, (iron deficiency anemia, folic acid pure red cel...

BLOOD DISORDERS 3 Inadequate dietary supply of nutrients Bone marrow failure (aplastic anemia, (iron deficiency anemia, folic acid pure red cell aplasia) deficiency anemia, and vitamin B12 deficiency anemia). ANEMIA OF DIMINISHED ERYTHROPOIESIS Myelophthisic anemia (Bone marrow infiltration by Anemia of chronic inflammation tumor or inflammatory cells limiting the BM ability to produce RBCs and other lines of cells) The bone marrow consists of progenitor cells in the myeloid, erythroid, and megakaryocytic lines. Erythroid stem cells produce RBCs. Myeloid precursors form WBCs. Megakaryocytes produce platelets. In anemia, reduced erythroid precursors affect RBCs. If pancytopenia occurs, at least two lines (erythroid, myeloid, or megakaryocytic) are affected, reducing RBCs, WBCs, and platelets. Iron Deficiency Anemia Most common nutritional deficiency in the World -80% of body iron is present in hemoglobin circulating in RBCs. -15-20% of body’s iron stored as ferritin & hemosiderin in organ s like (liver, BM, spleen, skeletal muscle). By taking a blood sample, we can measure iron levels through the following indices: 1-Serum ferritin level is a good measure of iron stores. 2-Transferrin saturation (carrier of iron in the blood), serum iron level, total iron binding capacity. -20% of heme iron (derived from animal sources like red meat) and 1-2% of nonheme iron (present in vegetarian resources) are absorbable. So, animal sources of iron are higher absorbed by the body than plant’s sources. - Main absorption site for iron in the body: duodenum, first part of small bowel. Causes iron deficiency anemia is always a sign of underlying disease; it’s not a disease by itself. ❑ Chronic blood loss: most important in westeirn world. -->Underlying causes: peptic ulcers, colon cancer, hemorrhoids, menorrhagia(Excessive blood loss during) menstruation, metrorrhagia(Bleeding between menstrual periods.), endometrial cancer ❑ Low intake and poor bioavailability of iron: in developing countries --->infants, elderly, teenagers, poverty ❑ Increased demands: pregnancy, infancy (the first year of life the baby needs more iron, so he is at risk for iron deficiency. Specially because milk interferes with the absorption of iron, which is the main source of food for infants) ❑ Malabsorption: celiac disease or after gastrectomy (because the gastric acid is an important factor to make the iron ready for absorption by small intestine.) we should always know the underlying cause because if the problem is malabsorption the patient will not benefit from taking oral iron, they should be given parenteral iron or intravascular injections Characteristics ~ Insidious (slow onset). ~ Iron stores depleted first (in the bone marrow, liver and spleen)>> declined serum ferritin >> absence of stainable iron in BM if we take a BM biopsy >> decrease in serum iron >> low transferrin saturation >> increased total iron-binding capacity to transferrin.(because we don’t have much iron, so the iron we have left will attach to the transferrin) ~ Capacity to synthesize proteins that contain iron like hemoglobin, myoglobin is diminished Clinical features -Mild and asymptomatic - Microcytic--> low MCV hypochromic anemia--> low - Weakness and pallor (non-specific sign and symptoms Hb+ increased central pallor. of anemia). - Poikoilocytosis (red blood cells with abnormal shapes) - Pica: consume nonfood stuffs such as dirt or clay - Platelets elevated. (especially in children) - Erythropoietin levels elevated because the reduced - Thinning, flattening, and spooning of fingernails. hemoglobin will stimulate the kidney to produce - Impaired work & cognition. erythropoietin. - Reduced immunocompetence. - Marrow response to erythropoietin is blunted because there is no iron, low reticulocytes unlike hemolyticanemia anemia  As you can see the RBCs are smaller Absent iron stain in BM than normal (microcytic) Also there is increased central pallor and peripheral small red remaining in the RBCs (hypochromic) Megaloblastic Anemias - Folate deficiency and vitamin B12 deficiency. - Folate and vit. B12 are required for DNA synthesis (thymidine synthesis) -Synthesis of RNA and cytoplasm proceeds at a normal rate, so the amount of cytoplasm is increased. -Nuclear/cytoplasmic asynchrony.(large immature erythroid precursors in the BM or RBCs in the peripheral blood) -Ineffective hematopoiesis (die in BM because they have abnormal nuclear maturation) - Most patients present with pancytopenia (anemia, thrombocytopenia, and granulocytopenia). Because vitamin B12 is also important in the nuclear maturation of megakaryocytes and myeloid precursors -Vitamin B12 is essential for myelin synthesis (anemia and neurologic disease) This is the main difference between vit. B12 and folate deficiency, in which folate deficiency doesn’t have neurological manifestations Morphology BM: Hypercellular with megaloblasts, giant granulocyte precursors and large bizarre megakaryocytes. Bone marrow increases cell production, but cells die there (ineffective erythropoiesis), leading to no rise in peripheral blood cells. ❑ Blood film: ▪ hyper-segmented neutrophils (5 or more lobes). ▪ macrocytic RBCs ❑ High MCV > 110 Macrocytic RBC, Hyper-segmented neutrophil with more than 5 lobes Folate Deficiency Anemia Causes: ❑ Poor diet (poor, infants, and elderly) ❑ Increased metabolic needs (pregnancy and chronic hemolysis (sickle cell anemia) Proliferation rate --> folate needed -->folate deficiency ❑ Problems with absorption (acidic food, drugs (phenytoin), celiac disease-->Folate is absorbed in the duodenum, so it’s affected by celiac disease (like iron ) ❑ Problems with metabolism (taking methoterexate) (chemotherapeutic agent) -Absent neurologic manifestations - Sore tongue Folate is present in many food resources, but it’s highly sensitive to cooking so it will be destroyed......body cannot store it for a long time Vitamin B12 (Cobalamin) Deficiency Anemia - Complex absorption: it needs the gastric acidity, pancreatic enzymes, and to bind with Intrinsic factor (produced from parietal cells of the stomach), intrinsic factor–B12 complexes pass to the distal ileum to be absorbed. - Liver reserve adequate amount of vitamin B12 for 5-20 years.(unlike folate) - Demyelination of the posterior and lateral columns of the spinal cord (Neurological manifestations) - Folate administration can reverse anemia BUT NOT neurologic symptoms. Causes: - Virtually never caused by inadequate intake (except vegetarians). Because it’s present in many animal food resources - Most frequent cause is malabsorption due to pernicious anemia (autoimmune atrophic gastritis) which cause destruction of parietal cells in the stomach so there won’t be production of intrinsic factor, and no absorption - Other causes : - Gastrectomy because gastric juices are important for absorption process and the parietal cells are important in the synthesis of the intrinsic factor. - Ileal resection because it’s the site of vitamin B12 absorption -Crohn disease that affects the ileum, so patient with inflammation of this part will have malabsorption. -Elderly Clinical features -As in other anemias (weakness, fatigability and pallor) -Beefy red tongue.(folate and vit. B12 are important for the maturation of epithelial cells lining the tongue) -Spinal cord disease (symmetric numbness, tingling, and burning in the feet or hands >> unsteadiness of gait and loss of position sense if severe). -Low serum vitamin B12 levels/ Normal folate levels -Macrocytic anemia high MCV Intramuscular B12 is used for a rapid bone marrow response, boosting reticulocyte count. This indicates -Leukopenia with hypersegmented granulocytes in the peripheral blood bone marrow recovery and normal RBC production -Dramatic reticulocyte response to parenteral (intravenous) vitamin B12.. Aplastic Anemia ❑ Multipotent myeloid stem cells in the BM are suppressed (it affects erythroid precursors, myeloid precursors and megakaryocytes) >> bone marrow failure and pancytopenia( thrombocytopenia, granulocytopenia and anemia). ❑ Causes: ❑ Extrinsic immune-mediated suppression of marrow progenitors (drugs, infections, viruses, toxins, radiation, environmental insults) ✓ Activated TH1 cells produce cytokines that kill hematopoietic progenitors ✓ Immunosuppressive Tx against T cells restores hematopoiesis in 60-70%. ❑ Intrinsic abnormality of stem cells. ✓ 5-10% of patients have inherited defects in telomerase (this will lead to progressive shortening of telomers in their DNA and cause premature senescence) Most of the cases of aplastic anemia are attributed to extrinsic immune-mediated suppression of marrow progenitors. Clinical features. 1- Pancytopenia (every single line is affected in the bone marrow) 2- Slowly progressive anemia 3- Thrombocytopenia >> petechiae, ecchymoses and bleeding 4- Neutropenia >> serious infections. 5- Examination of the BM is mandatory to rule out other causes of pancytopenia Hypocellular BM in aplastic anemia When bone marrow is replaced by fat, hematopoiesis decreases, leading to reduced blood cell production. Anemia of Chronic Inflammation - The most common anemia in hospitalized patients. - Suppressed erythropoiesis by systemic inflammation - In the setting of: - Chronic microbial infections like TB - Chronic immune disorders like Rheumatoid arthritis - Neoplasms or tumor cancers. Pathogenesis: 1) High levels of plasma hepcidin from the liver (induced by IL-6) >> blocks the transfer of iron to erythroid precursors.(the iron become sequestered in the BM macrophages) 2) Chronic inflammation impair erythropoietin synthesis by the kidney. - Administration of erythropoietin and iron can improve the anemia - Cured by treating the underlying disease. Clinical features: ~ Similar to IDA (iron deficiency anemia, because the main principle is that iron isn’t delivered to the precursors in the bone marrow) in ~ Serum iron levels usually are low ~ Hypochromic microcytic. ~ Low reticulocytes. Different from IDA: - Stored iron ferritin are increased (so iron will be inside the macrophages in BM and serum bone marrow), total iron-binding capacity is reduced. Iron stain in BM if you perform an iron stain in the bone marrow it will be increased, the blue is the iron in the bone marrow Myelophthisic Anemia ~ Extensive infiltration of BM by tumors or other lesions (like inflammation or granulomas) ~ Most commonly associated with metastatic diseases (breast, lung, or prostate cancers (the cancer cells will replace the bone marrow cells) ~ Advanced tuberculosis (the BM cells will be replaced by granulomas) ~ Misshapen red cells (resembling teardrops) appear on blood film. ~ Pancytopenia.