Anaemia of Chronic Disease & Megaloblastic Anemia PDF

Anaemia of chronic disease • • • • • • • • we said whentheres ii iiii iiq a.nu One of the most common types of anaemia that associated with different diseases like infections, chronic inflammatory diseases, chronic renal failure and malignant diseases. Pathogenesis is related to decreased rel...

Anaemia of chronic disease • • • • • • • • we said whentheres ii iiii iiq a.nu One of the most common types of anaemia that associated with different diseases like infections, chronic inflammatory diseases, chronic renal failure and malignant diseases. Pathogenesis is related to decreased release of iron from macrophages (high hepcidin), reduced RBC life span, inadequate erythropoietin response to anaemia. Mild non-progressive anaemia (rarely Hb < 9 gm/dl), and the severity related to illness severity. Normochromic normocytic or mildly hypochromic red cells. Low serum iron and low TIBC. usuayinirndificiency is low Normal or high serum ferritin. Whenserumiron buthere high be will High C-reactive protein and high ESR. Type but itsnot irons red High serum Hepcidin level. No the willbe to tianya.fi available soTIBS ifeng.EE Megaloblastic anemia • Anemia due to impaired DNA synthesis, result mainly from B12 and e Folate deficiency. • All haemopoietic cell lines (erythropiesis, granulopoiesis, megakaryopoiesis) can be affected resulting in severe anemia and even pancytopenia. reduce productionof An celllines WBCRBCplatelets • The hallmark is enlargement of BM erythroid precursors (megaloblast) giving rise to abnormal large RBC in blood (macrocytes), in addition to giant granulocytic precursors in BM yielding hypersegmented neutrophils in peripheral blood. we • It is a serious disease that can cause neurological and psychiatric abnormalities which are preventable and reversible in the early stage of disease. maturation of divide can't to Grow but able erythroblast relativeto cytoplasm nucleus use of delayed B12 (cobalamin) • Forms of B12:Methylcobalamin is the main form in human body, Cyanocobalamin, form use in investigations, Hydroxycobalamin, form use in treatment. • Human is unable to synthesis B12 so requires intake. • It is present only in food of animal origin specially meat, liver and fish and less in dairy products. • It is a heat stable vitamin. • Vegetables and fruits free of B12.mind • Daily requirment is about 1- 2 µg. • Body store about 2-3 mg. (2-4 years) Functions of vitamin B12 B12 in involved in two important Biochemical reactions: 1. Conversion of Homocystiene to Methionine, and this is essential for maintaining the active form of folate inside the cells to be available for DNA synthesis. 2. Conversion of Methylmalonyl-Co A into succinyl-Co A, and this requires Deoxyadenosyl-cobalamin form, and involved in the synthesis of myelin in the CNS. thatswhy the neurological complication of I associated megaloblasticAnemiais only deficiency deficiency Not withBI folic Absorption of B12 in the ileum pass through some steps: • In stomach: B12 bind to R-binder which is produced by saliva and gastric juice. to protect Brfrom brakingTown • In duodenum: Digestion of this complex occurs by pancreatic enzymes, then the B12 will bind to Intrinsic factor (IF) which is a secreted from stomach parietal cells. • In terminal ileum: IF bind to specific receptor (Cubilin) for absorption and B12 appear in portal circulation after 6 hrs attached to transcobalamin-II (TC II). Go take BR to Bone marrowfor heckh thesis Causes of vitamin B12 deficiency: (1) Malabsorption (main cause) like: oGastric causes, as pernicious anemia, gastrectomy. oIntestinal causes, as ileal resection, blind loop syndrome, (2) Dietary deficiency: as in vegans (3) B12 abnormal metabolism as TC II and IF deficiency. Folic acid • Human is unable to synthesis FA, most foods contain FA, specially liver, green vegetables, fruits and nuts, it is destroyed by heating. • Absorption takes place in upper half of small intestine (deudenum and jejunum) • Daily requirment about 100-150 µg. morhishfranp.in • Body store 10-12 mg.(4 months) • Function of folate As a co-enzyme in purine and pyrimidine synthesis Causes of FA deficiency: (1)Inadequate dietary intake (common cause due to low storage state): old age, poverty, alcoholism, psychiatric disturbance. (2)Malabsorption like celiac disease. needed is (3)Increase utilization: Mff -Physiological as pregnancy, lactation, prematurity -Pathological as hemolytic anemia, malignancy, inflammatory disease. 1 7 (4) Antifolate drugs as anti-convulsants. (5) Liver diseases. Biochemical basis of MBA: •MBA is a type of anemia characterized by impaired DNA synthesis. •DNA synthesis requires polymerization of 4 deoxyribonucleoside triphosphates, and FA deficiency impaires thymidylate synthesis which is a crucial step in DNA synthesis as this step need methylin THF polyglutamate. •B12 required to achieve the active form of folate inside the cells. •So deficiency of any vitamin will lead to impair in DNA synthesis. if EE imonuenn essentialp fgi i dgtf Clinical features of MBA • May be asymptomatic. • Usually insidious onset with signs and symptoms of anemia. • Mild jaundice (due to intramedullary destruction of red cell deÉÉÉf precursors). theorknormid destructingBonemarrow • Epithelial tissue changes as glossitis and angular stomatitis. • NTD (neural tube defect ) in FA deficiency and may occur with B12 deficiency. Ñ D • Neurological manifestations only with B12 deficiency due to defect in methylation of myelin, it is usually symmetrical affecting lower limbs more. • Psychiatric abnormality. Pernicious anemia • It is MBA due to B12 deficiency • It is caused by autoimmune attack on gastric mucosa • characterized by gastric atrophy, with plasma cell and lymphoid infiltrate in lamina properia in the wall of stomach • reduced or absent intrinsic factor with achlorhydria. • It is more in females, mostly a disease of the elderly, more in patients with autoimmune mediated disorders like autoimmune thyroid disease. • Increased risk of gastric carcinoma 2-3%. • Not common in Iraq, common in north Europe. • Mostly it is autoimmune in nature with presence of serum antibodies like anti-IF Ab, anti-parietal cells Ab and anti-gasrtin receptor Ab. Laboratory findings of MBA: Hematological findings: imacroiy.li •Variable degree of anemia, may be severe Hb < 6 gm/dl. •MCV increased >100 fl, may be up to 135 fl. •Increase MCV, MCH, and normal MCHC. •Increase RDW. •Low retic count. •Leucocytes may be reduced, platelets may be moderately reduced (pancytopenia). •Blood film: oval macrocytes, hypersegmented neutrophils, leukoerythroblastic picture may found. c E Other investigations: • low Serum B12, low serum FA. • Therapeutic trials of both vitamins and assess the response by increase Hb and retic count after several days. • High S. LDH, indirect hyperbilirubinaemia due to intramedullary destruction of red cell precursors. . Search and exclude causes for B12 and FA. • Serum Ab measuring and gastric biopsy in suspected cases of pernicious anemia. • BM findings: Hypercellular marrow, Erythroid hyperplasia, with megaloblastic maturation. Giant metamyelocytes, Abnormal megakryocyte nuclear segmentation Normochromic, Anisocytosis poikilocytosis, macrocytosis, tear drop cells oval Hypersegmented Neutrophiles cellsare very an egghead Normoblastic & Megaloblastic Erythropoiesis Response to treatment: • • • • Initial correction of patient behavior and appetite within 1-2 days. Retic count increase with peak level at 7 days. was Hb level increase 1 gm/dl /wk . if thetreatment Peripheral neuropathy may partially improve but spinal cord damage is irreversible. good Anaemia of chronic disease • • • • • • • • we said whentheres ii iiii iiq a.nu One of the most common types of anaemia that associated with different diseases like infections, chronic inflammatory diseases, chronic renal failure and malignant diseases. Pathogenesis is related to decreased release of iron from macrophages (high hepcidin), reduced RBC life span, inadequate erythropoietin response to anaemia. Mild non-progressive anaemia (rarely Hb < 9 gm/dl), and the severity related to illness severity. Normochromic normocytic or mildly hypochromic red cells. Low serum iron and low TIBC. usuayinirndificiency is low Normal or high serum ferritin. Whenserumiron buthere high be will High C-reactive protein and high ESR. Type but itsnot irons red High serum Hepcidin level. No the willbe to tianya.fi available soTIBS ifeng.EE Megaloblastic anemia • Anemia due to impaired DNA synthesis, result mainly from B12 and e Folate deficiency. • All haemopoietic cell lines (erythropiesis, granulopoiesis, megakaryopoiesis) can be affected resulting in severe anemia and even pancytopenia. reduce productionof An celllines WBCRBCplatelets • The hallmark is enlargement of BM erythroid precursors (megaloblast) giving rise to abnormal large RBC in blood (macrocytes), in addition to giant granulocytic precursors in BM yielding hypersegmented neutrophils in peripheral blood. we • It is a serious disease that can cause neurological and psychiatric abnormalities which are preventable and reversible in the early stage of disease. maturation of divide can't to Grow but able erythroblast relativeto cytoplasm nucleus use of delayed B12 (cobalamin) • Forms of B12:Methylcobalamin is the main form in human body, Cyanocobalamin, form use in investigations, Hydroxycobalamin, form use in treatment. • Human is unable to synthesis B12 so requires intake. • It is present only in food of animal origin specially meat, liver and fish and less in dairy products. • It is a heat stable vitamin. • Vegetables and fruits free of B12.mind • Daily requirment is about 1- 2 µg. • Body store about 2-3 mg. (2-4 years) Functions of vitamin B12 B12 in involved in two important Biochemical reactions: 1. Conversion of Homocystiene to Methionine, and this is essential for maintaining the active form of folate inside the cells to be available for DNA synthesis. 2. Conversion of Methylmalonyl-Co A into succinyl-Co A, and this requires Deoxyadenosyl-cobalamin form, and involved in the synthesis of myelin in the CNS. thatswhy the neurological complication of I associated megaloblasticAnemiais only deficiency deficiency Not withBI folic Absorption of B12 in the ileum pass through some steps: • In stomach: B12 bind to R-binder which is produced by saliva and gastric juice. to protect Brfrom brakingTown • In duodenum: Digestion of this complex occurs by pancreatic enzymes, then the B12 will bind to Intrinsic factor (IF) which is a secreted from stomach parietal cells. • In terminal ileum: IF bind to specific receptor (Cubilin) for absorption and B12 appear in portal circulation after 6 hrs attached to transcobalamin-II (TC II). Go take BR to Bone marrowfor heckh thesis Causes of vitamin B12 deficiency: (1) Malabsorption (main cause) like: oGastric causes, as pernicious anemia, gastrectomy. oIntestinal causes, as ileal resection, blind loop syndrome, (2) Dietary deficiency: as in vegans (3) B12 abnormal metabolism as TC II and IF deficiency. Folic acid • Human is unable to synthesis FA, most foods contain FA, specially liver, green vegetables, fruits and nuts, it is destroyed by heating. • Absorption takes place in upper half of small intestine (deudenum and jejunum) • Daily requirment about 100-150 µg. morhishfranp.in • Body store 10-12 mg.(4 months) • Function of folate As a co-enzyme in purine and pyrimidine synthesis Causes of FA deficiency: (1)Inadequate dietary intake (common cause due to low storage state): old age, poverty, alcoholism, psychiatric disturbance. (2)Malabsorption like celiac disease. needed is (3)Increase utilization: Mff -Physiological as pregnancy, lactation, prematurity -Pathological as hemolytic anemia, malignancy, inflammatory disease. 1 7 (4) Antifolate drugs as anti-convulsants. (5) Liver diseases. Biochemical basis of MBA: •MBA is a type of anemia characterized by impaired DNA synthesis. •DNA synthesis requires polymerization of 4 deoxyribonucleoside triphosphates, and FA deficiency impaires thymidylate synthesis which is a crucial step in DNA synthesis as this step need methylin THF polyglutamate. •B12 required to achieve the active form of folate inside the cells. •So deficiency of any vitamin will lead to impair in DNA synthesis. if EE imonuenn essentialp fgi i dgtf Clinical features of MBA • May be asymptomatic. • Usually insidious onset with signs and symptoms of anemia. • Mild jaundice (due to intramedullary destruction of red cell deÉÉÉf precursors). theorknormid destructingBonemarrow • Epithelial tissue changes as glossitis and angular stomatitis. • NTD (neural tube defect ) in FA deficiency and may occur with B12 deficiency. Ñ D • Neurological manifestations only with B12 deficiency due to defect in methylation of myelin, it is usually symmetrical affecting lower limbs more. • Psychiatric abnormality. Pernicious anemia • It is MBA due to B12 deficiency • It is caused by autoimmune attack on gastric mucosa • characterized by gastric atrophy, with plasma cell and lymphoid infiltrate in lamina properia in the wall of stomach • reduced or absent intrinsic factor with achlorhydria. • It is more in females, mostly a disease of the elderly, more in patients with autoimmune mediated disorders like autoimmune thyroid disease. • Increased risk of gastric carcinoma 2-3%. • Not common in Iraq, common in north Europe. • Mostly it is autoimmune in nature with presence of serum antibodies like anti-IF Ab, anti-parietal cells Ab and anti-gasrtin receptor Ab. Laboratory findings of MBA: Hematological findings: imacroiy.li •Variable degree of anemia, may be severe Hb < 6 gm/dl. •MCV increased >100 fl, may be up to 135 fl. •Increase MCV, MCH, and normal MCHC. •Increase RDW. •Low retic count. •Leucocytes may be reduced, platelets may be moderately reduced (pancytopenia). •Blood film: oval macrocytes, hypersegmented neutrophils, leukoerythroblastic picture may found. c E Other investigations: • low Serum B12, low serum FA. • Therapeutic trials of both vitamins and assess the response by increase Hb and retic count after several days. • High S. LDH, indirect hyperbilirubinaemia due to intramedullary destruction of red cell precursors. . Search and exclude causes for B12 and FA. • Serum Ab measuring and gastric biopsy in suspected cases of pernicious anemia. • BM findings: Hypercellular marrow, Erythroid hyperplasia, with megaloblastic maturation. Giant metamyelocytes, Abnormal megakryocyte nuclear segmentation Normochromic, Anisocytosis poikilocytosis, macrocytosis, tear drop cells oval Hypersegmented Neutrophiles cellsare very an egghead Normoblastic & Megaloblastic Erythropoiesis Response to treatment: • • • • Initial correction of patient behavior and appetite within 1-2 days. Retic count increase with peak level at 7 days. was Hb level increase 1 gm/dl /wk . if thetreatment Peripheral neuropathy may partially improve but spinal cord damage is irreversible. good