Blood and Lymphatic System Lecture 2 (2024) PDF

Blood and Lymphatic System Dr. Raya D. Marji, M.D. Al-Balqa Applied University Office: O505  => aciti,s I -> -S Abs sd XIAD's...

Blood and Lymphatic System Dr. Raya D. Marji, M.D. Al-Balqa Applied University Office: O505  => aciti,s I -> -S Abs sd XIAD's vascular -> extra 35 &  -esssisy I bloods.Shee -> -iss Eis ~ Immunohemolytic Anemia Antibodies that bind to determinants on red cell membranes. Spontaneously or induced by exogenous agents. Classification: 1. The nature of the antibody. 2. The presence of predisposing conditions. Direct Coombs test >> then indirect Coombs test. Warm Antibody Immunohemolytic Anemia: Results from the binding of high-affinity autoantibodies to red cells, which are then removed from the circulation by phagocytes. Erythrophagocytosis, spherocytes.& Immunoglobulin G (IgG) or (rarely) IgA antibodies that are active at 37°C. More than 60% of cases are idiopathic (primary), whereas another 25% are secondary to an underlying immunologic disorder. Most patients have chronic mild anemia and moderate splenomegaly and require no treatment. Cold Antibody Immunohemolytic Anemia: Low-affinity IgM antibodies, at temperatures below 30°C. Distal parts of the body in cold weather. Hemolysis is mainly extravascular. Binding of pentavalent IgM also crosslinks red cells and causes them to clump (agglutinate). Raynaud phenomenon.  Mechanical forces: 1. Traumatic Hemolysis: Defective cardiac valve prostheses. Activity involving repeated physical pounding of one or more body parts. ig & 2. Microangiopathic hemolytic anemia: small vessels become partially obstructed or narrowed by lesions that predispose passing red cells to mechanical damage: ✓Disseminated intravascular coagulation (DIC). ✓Malignant hypertension. ✓Systemic lupus erythematosus. ✓Thrombotic thrombocytopenic purpura (TTP). ✓Hemolytic uremic syndrome (HUS). ✓Disseminated cancer. Mechanical fragmentation of red cells (schistocytosis) leads to the appearance of characteristic “burr cells,” “helmet cells,” and “triangle cells” in peripheral blood smears. Microangiopathic hemolytic anemia- Peripheral smear Paroxysmal Nocturnal Hemoglobinuria (PNH): Acquired mutations in PIGA gene. The pathogenic mutations in PNH occur in an early hematopoietic progenitor. lysis &II SII,*;se's is 1 (85 ses Red cells are sensitive to lysis by the complement C5b-C9 membrane attack complex. Enhanced by the decrease in blood pH that accompanies sleep. Anemia and iron deficiency resulting from chronic intravascular hemolysis. The most feared complication is thrombosis. All treated patients must be vaccinated against N. meningococcus. Malaria: Malaria It is estimated that malaria affects 500 million and kills more than 1 million people per year. Endemic in Asia and Africa. One of five types of protozoa; Plasmodium falciparum. Plasmodium malariae, Plasmodium vivax, Plasmodium knowlesi, and Plasmodium ovale. Transmitted by the bite of female Anopheles mosquitoes. Fatal falciparum malaria often involves the small vessels of the brain, a complication known as cerebral malaria. Malaria: MORPHOLOGY: Characteristic brown malarial pigment derived from hemoglobin called hematin is released from the ruptured red cells and produces discoloration of the spleen, liver, lymph nodes, and bone marrow. Activation of defense mechanisms in the host leads to a marked hyperplasia of mononuclear phagocytes, producing massive splenomegaly and occasional hepatomegaly Malaria: Hemoglobinopathies: A group of hereditary disorders caused by inherited mutations that lead to structural abnormalities in hemoglobin  -> hemolysis simi - -> inni 95. es stickysisabor; S ↳ ② - ⑬ pogarize the  ·x i s , abige I foot), hand isbone, infarctions sngsinlet -8. stration · ji " - Sickle cell anemia ↳ Caused by a mutation in β-globin that creates sickle hemoglobin S (HbS). The most common familial hemolytic anemia. -41s: In parts of Africa where malaria is endemic, the gene frequency approaches 30% as a result of a protective effect against S Plasmodium falciparum malaria. In the United States, approximately 8% of blacks are heterozygous HbS carriers and about 1 in 600 have sickle cell anemia. Pathogenesis:q Single amino acid substitution in β-globin that results in a tendency for deoxygenated HbS to self-associate into polymers. & Normal hemoglobins are tetramers composed of two pairs of similar chains. On average, the normal adult red cell contains 96% HbA (α2β2), 3% HbA2 (α2δ2), and 1% fetal Hb (HbF, α2γ2). In patients with sickle cell anemia, HbA is completely replaced by HbS, whereas in heterozygous carriers, only about half is replaced. HbS differs from HbA by having a valine residue instead of a glutamate residue at the 6th amino acid position in β-globin. On deoxygenation HbS molecules undergo a conformational change that allows polymers to form via intermolecular contacts involving the abnormal valine residue. These polymers - distort the red cell, which assumes an elongated crescentic, or sickle, shape. Membrane distortion leads to an influx of calcium, which causes the loss of potassium and water and also damages the membrane skeleton.  Three factors are particularly important in determining whether clinically significant polymerization of HbS occurs in patients: 1. The intracellular levels of hemoglobins other than HbS. 2. The intracellular concentration of HbS. 3. The time required for red cells to pass through the microvasculature. Major pathologic consequences: 1- Chronic moderately severe hemolytic anemia: The mean life span of red cells in sickle cell anemia averages only 20 days, and the severity of the hemolysis correlates with the fraction of irreversibly sickled cells that are present in the blood. 2- Vascular obstructions, which result in ischemic tissue damage and pain crises. Result from superimposed factors such as infection, inflammation, dehydration, and acidosis. MORPHOLOGY: Peripheral smears: elongated, spindled, or boat-shaped irreversibly sickled red cells. Hypoxia-induced fatty changes in the heart, liver, and renal tubules. Compensatory hyperplasia of erythroid progenitors in the marrow with bone resorption and secondary new bone formation, “crewcut” in radiographs. Extramedullary hematopoiesis may appear in the liver and spleen. In children there is moderate splenomegaly (splenic weight up to 500 g) due to red pulp congestion caused by entrapment of sickled red cells. Chronic splenic erythrostasis produces hypoxic damage and infarcts (autosplenectomy) Vascular congestion, thrombosis, and infarction can affect any organ, including the bones, liver, kidney, retina, brain, lung, and skin. 35-55/ Priapism: can lead to penile fibrosis and erectile dysfunction. Hemolytic anemias, hemosiderosis and pigment gallstones are common. Sickle cell anemia:  Clinical Features: 845, Unremitting course with sudden crises. Homozygous sickle cell disease usually is asymptomatic until 6 months of age when the shift from HbF to HbS is complete. The anemia is moderate to severe; most patients have hematocrits of 18% to 30% (normal range, 38%–48%). the Hyperbilirubinemia and compensatory reticulocytosis. Hemosi de, bilirubin Vasoocclusive crises: 3 1. Hand-foot syndrome: infarction of bones in the hands and feet, is the most common presenting symptom in young children. 2. Acute chest syndrome: sluggish blood flow in inflamed lung (e.g., an area of pneumonia) leads to sickling within hypoxemic pulmonary beds. 3. Stroke: together with the acute chest syndrome are the two leading causes of ischemia- related death. 4. Proliferative retinopathy: visual acuity and blindness -x53,5-  Aplastic crisis: sudden decrease in red cell production, triggered by the infection of erythroblasts by parvovirus B19. Infections: encapsulated bacteria, such as pneumococci. Salmonella osteomyelitis. The diagnosis is confirmed by electrophoretic demonstration of HbS. Prenatal diagnosis: fetal DNA obtained by amniocentesis or biopsy of chorionic villi. Treatment: Approximately 50% of patients now survive beyond the fifth decade. Prophylactic treatment with penicillin to prevent pneumococcal infections. Hydroxyurea: reduces pain crises and lessens the anemia through several effects, including (1) an increase in levels of HbF; (2) an anti-inflammatory effect because of the inhibition of white cell production; (3) an increase in red cell size, which lowers the intracellular hemoglobin concentration; and (4) its metabolism to NO, a potent vasodilator and inhibitor of platelet aggregation. Allogeneic bone marrow transplantation I 5 S: BMSI - , 5: & ↓ Bhatins -  X x X x x x x+ xx - 8. -5 chromoso chromosome Do, Bts ever ↳ Bi] less sever  -H iam sin Thalassemia Inherited disorders caused by mutations in globin genes that decrease the synthesis of α- or β-globin. Unpaired “normal” globin chains. Common in Mediterranean, African, and Asian regions. Autosomal codominant. Adult hemoglobin, or HbA, is a tetramer composed of two α chains and two β chains. The α chains are encoded by two α-globin genes on chromosome 16. The β chains are encoded by a single β-globin gene located on chromosome 11. β-Thalassemia: Mutations associated with β-thalassemia fall into two categories: 1. β0 , in which no β-globin chains are produced. 2. β+ , in which there is reduced (but detectable) β-globin synthesis. One abnormal allele have β-thalassemia minor (also known as β- thalassemia trait), which is asymptomatic or mildly symptomatic. Inheriting any two β0 and β+ alleles have β-thalassemia major. Inadequate HbA formation, resulting in small (microcytic), poorly hemoglobinized (hypochromic) red cells. · is Accumulation of unpaired α-globin chains, which form toxic precipitates that severely damage the membranes of red cells and erythroid precursors. Ineffective erythropoiesis: leads to inappropriate increase in the absorption G' of dietary iron, which without medical intervention inevitably leads to iron overload. & - iron is; 6 gebl isit (1952, : iron i- RBC II ·iron overload S.; six IS, iron o 88 295.99;13- 51 α-Thalassemia: Deletions involving one or more of the α-globin genes. The severity of the disease is proportional to the number of α- globin genes that are deleted. MORPHOLOGY: Confined to the peripheral blood. Microcytic, hypochromic RBC, regular in shape. Target cells. Thalassemia major: Marked microcytosis, hypochromia, poikilocytosis (variation in cell shape), and anisocytosis (variation in cell size). Nucleated red cells (normoblasts) are also seen that reflect the underlying erythropoietic drive. β-Thalassemia intermedia and HbH disease are associated with peripheral smear findings that lie between these two extremes. ‫ڡﺲ كﻞ اﳾ‬#‫ٮ‬#‫ڡﺲ اﻻﻋراض و‬#‫ٮ‬# ‫ڡﺤﺼﻬﺎ‬#‫ٮ‬#‫ٮﻪ دم و‬#‫ٮ‬,‫ﺣﺬ ﻋ‬#‫ٮﻮ‬# ‫ٮﺺ ﻟﻤﺎ‬,‫ﺤ‬#‫ٮﺸ‬%‫ٮﺎﻟ‬- ‫ٮﻬوا‬-‫ٮﺸﺎ‬%‫ٮ‬- hbH ‫ وال‬intermedia ‫ٮﻪ ال‬#‫ى ا‬1‫ٮﺤك‬%‫ٮ‬- ‫ٮﻪ‬,‫ٮ‬#‫ڡﻄﻪ اﻟ)ٮﺎ‬%‫ٮ‬#‫ﻟ‬ Hyperplasia of erythroid progenitors, with a shift toward early forms. The expanded erythropoietic marrow may completely fill the intramedullary space of the skeleton, invade the bony cortex, impair bone growth, and produce skeletal deformities. Extramedullary hematopoiesis and hyperplasia of mononuclear phagocytes result in BM & RBCs SI I prominent splenomegaly, hepatomegaly, and lymphadenopathy. s1, &5.5- RBC i5 918s. 81 ISthalasemias? RBCs BM S1 I1 medulla (1s Medulla 31 I Growth retardation and hemosiderosis. : 891s5, Bone deformities - nee d destruction of RBCs SIsspleens hemosidrens $5. HB Thalassemia:  Clinical Features: β-Thalassemia trait and α-thalassemia trait: asymptomatic, Mild microcytic hypochromic anemia; normal life expectancy. β-Thalassemia major: growth retardation, sustained by blood transfusions. - 20 30 With transfusions alone, survival into the second or third. Iron overload: cardiac dysfunction from secondary robsre hemochromatosis, fatal. Hematopoietic stem cell transplantation at an early age is the B treatment of choice. Diagnosis: si patient 8l8 ;51 6elg β-thalassemia major can be strongly suspected on clinical grounds. Hb electrophoresis shows a profound reduction or absence of HbA and increased levels of HbF. The HbA2 level may be normal or increased. -45'54 Prenatal diagnosis of β-thalassemia: specialized centers by DNA analysis. β-thalassemia minor: reduced level of HbA (α2β2) and an increased level of HbA2 (α2δ2). HbH disease can be diagnosed by detection of β4 tetramers by electrophoresis.