Blood and Lymphatic System Lecture 1 Slides PDF

Blood and Lymphatic System Dr. Raya D. Marji, M.D. Al-Balqa Applied University Office: O505  Disorders RBC of red Nonfunction MRBC cells: ~ IDA ↓Ab ⑧ Anemia - or polycythemia. --...

Blood and Lymphatic System Dr. Raya D. Marji, M.D. Al-Balqa Applied University Office: O505  Disorders RBC of red Nonfunction MRBC cells: ~ IDA ↓Ab ⑧ Anemia - or polycythemia. -- ↑ RBC XBC, Anemia: reduction in the oxygen-transporting capacity of blood, resulting from a decrease in the red cell mass to subnormal levels. BM NRBC Anemia can stem from=> bleeding, increased red cell destruction, or BM fait - mytic decreased red cell production. anemia Triggers increased production of the growth factor erythropoietin>> extramedullary hematopoiesis. Reticulocytosis vs. Reticulocytopenia. cells - [Reticulate h - - - - ↓ i >1). IDA BM failure - - - &  100 mean corpuscular 80 - are ↓ -> nation - ⑳ it E =)4 = 0 #C - - XHBX - · X & Anemia chronic of disease - -- - Set is  ANEMIAS … GENERAL with megaloblasts D - a - & epigmented gallston Rubin Yellow) -- ↳ ARBC Wednesday, March 2, 2022 - spongy 5 Bones from GI -- ofiron &absorption easic  Ba ② Blood smear - count blood complete Red cell morphology. & The size, -- color, and shape of the red cells. - By visual inspection of peripheral smears and also are expressed quantitatively using the following indices: - 80 100 -- 1. Mean cell volume (MCV): the average volume per red cell, expressed in I femtoliters (cubic microns). => 2. Mean cell hemoglobin (MCH): the average mass of hemoglobin per red IDA cell, expressed in picograms. I - - - 3. Mean cell hemoglobin concentration (MCHC): the average concentration - of hemoglobin in a given volume of packed red cells, expressed in grams per deciliter. 4. Red cell distribution width (RDW): the coefficient of variation of red cell volume. - - - - - - Pathological classification of anemia 10 Wednesday, March 2, 2022 I  X Other blood tests: IDA IDA W v 1. Serum iron indices (iron levels, iron-binding capacity, & ⑧ transferrin saturation, and ferritin concentrations). -* 2. Plasma unconjugatedE dehydrogenase levels - bilirubin, haptoglobin, and lactate ↑ AB ⑧ 3. Serum and red cell folate and vitamin B12 concentrations. -- bilirubin E Sickle cell - 4. Hemoglobin electrophoresis. 5- - 5. The Coombs test. F - B-Analasmin H  CBC test it v wi  CLINICAL FEATURES OF ANEMIA The clinical consequences of anemia are determined by its -- severity, rapidity of onset, and underlying pathogenic mechanism. If the onset is slow: compensated for by increases in -- 4O_ cardiac output, - -respiratory rate, and red cell 2,3-diphosphoglycerate (DPG). C ↑affinity On - XHB X --- Pallor, fatigue, hyperbilirubinemia, jaundice, and pigment gallstones. Anemia that stems from ineffective hematopoiesis: inappropriate increases in iron absorption from the gut (secondary hemochromatosis). # Untreated severe congenital anemia such as β-thalassemia major inevitably results in growth retardation, skeletal abnormalities, andC cachexia. - - - X ↑  ANEMIA OF BLOOD LOSS: ↑ TIBC nysockium, HEMORRHAGE Acute bleeding or chronic blood loss. * tirone Normocytic and normochromic or iron deficiency anemia. => # crocytic ↑ I  201 80% -containg Emoglobinmyoglobin iron Iron Deficiency enzymes Catalase, Anemia: cy rochromes I The most common nutritional deficiency in the world and results in clinical signs and symptoms that are mostly related to anemia. About 10% of people living in developed countries and 25% to 50% of those in developing countries. The normal total body iron mass is about 2.5 g for women and 3.5 g for men. Approximately 80% of functional body iron is present in hemoglobin, with the Age remainder located in myoglobin and iron-containing enzymes (e.g., catalase, cytochromes). The iron storage pool, consisting of hemosiderin and ferritin-bound iron in the liver, spleen, bone marrow, and skeletal muscle, contains on average 15% to 20% of total body iron. Serum ferritin: iron stores. Bone marrow iron.  Iron is transported in the plasma bound to the protein transferrin. Transferrin is about 33% saturated with iron, yielding serum iron levels that average 120 µg/dL in men and 100 µg/dL in women. Thus, the normal total iron-binding capacity of serum is 300 to 350 µg/dL. Iron is lost at a rate of 1 to 2 mg/day through the shedding of mucosal and skin epithelial cells, and this loss must be balanced by the absorption of dietary iron, which is tightly regulated. The normal daily Western diet contains 10 to 20 mg of iron. Most is found in heme within meat and poultry, with the remainder present as inorganic iron in vegetables. About 20% of heme and 1% to 2% of nonheme iron are absorbable; hence, the average Western diet contains sufficient iron to balance fixed daily losses. Metabolism:. 0 C W - -I ⑳ 2 0 ⑧ 0 ⑧ - ↑X  Pathogenesis: 1. Chronic blood loss is the most important cause of iron deficiency anemia in the Western world. The most common sources of bleeding are the gastrointestinal tract (e.g., peptic ulcers, colon cancer, hemorrhoids) and the female genital tract (e.g., - menorrhagia, metrorrhagia, F 14 endometrial cancer). - 2. In the developing world, low intake and poor bioavailability because of predominantly L vegetarian diets are the most common causes of iron deficiency. (infants fed exclusively milk, in the impoverished, in the elderly, and in teenagers subsisting predominantly on junk food). - 3. Increased demands not met by normal dietary intake occur worldwide during pregnancy and - infancy. - - - 4. Malabsorption can occur with celiac disease or -- after gastrectomy. - Insidiously (Gradual onset) L Y Iron stores are depleted >> decline in serum ferritin and the absence of& stainable iron in the bone marrow. - Followed by a decrease - in serum iron and a rise in the serum transferrin. -  Clinical Features: Mild and asymptomatic. ⑧ Nonspecific manifestations, such as weakness, listlessness, and pallor. -- With long-standing anemia, abnormalities of the fingernails, including thinning, flattening, and “spooning,” may appear. - Neurobehavioral complication is pica. & In peripheral smears: microcytic and hypochromic. - - Iron Deficiency Anemia  Diagnostic criteria include: anemia, hypochromic and microcytic red cell indices. - low serum ferritin and iron levels. low transferrin saturation. & increased total iron-binding capacity. response to iron therapy. Platelet count often is elevated. Erythropoietin levels are elevated. Microcytic hypochromic anemia is not a disease but rather a symptom of some underlying disorder. * ANEMIA OF DIMINISHED ERYTHROPOIESIS: (1)Inadequate dietary supply of nutrients, particularly iron, folic acid, and vitamin B12. (2)Bone marrow failure (aplastic anemia), systemic inflammation (anemia of chronic inflammation), or bone marrow infiltration by tumor or inflammatory cells (myelophthisic anemia). failure  Megaloblasti c Anemias: DNAsis?thymdines, * DNA SI Folate deficiency and vitamin I -> si" is Cytoplasm B12 deficiency. asyncrony - 5:50 5835's Both vitamins are required for nucleus s. Si cytoplasm))5 - Is DNA synthesis. IDAcegis-st is 6, 1916 cytoplasms, 9.5,isd Microcytic  Pathogenesis: Megaloblastic anemia stems from metabolic defects that lead to inadequate biosynthesis of thymidine (required for DNA replication). Thymidine deficiency causes abnormalities in dividing cells throughout the body, but the hematopoietic marrow is most severely affected. I Because the synthesis of RNAM and cytoplasmic elements proceeds at a normal rate and thus outpaces that of the nucleus, the hematopoietic precursors show nuclear-cytoplasmic asynchrony. Pancytopenia (anemia, thrombocytopenia, and granulocytopenia).  MORPHOLO GY: 1- Bone marrow: hypercellular and contains numerous megaloblastic erythroid - pancytopenia & i proliferation- BMII 0 94 5.si progenitors. Megaloblasts are larger than normal erythroid progenitors (normoblasts) and have delicate, finely reticulated nuclear chromatin (indicative of nuclear immaturity). Giant metamyelocytes. Megakaryocytes may also be abnormally large and have bizarre multilobed nuclei. 2- Peripheral blood: The earliest change is the appearance of hypersegmented neutrophils. Red cells are large, eggshaped macroovalocytes. MCV often is greater than 110 fL (normal, 82–96 fL). Large, misshapen platelets. s Megaloblastic Anemia  to Be deficiency leads Folate (Folic Acid) Deficiency 512 deficiency usually Anemia: Inadequate dietary intake. Poor diet or increased metabolic needs. Deficiency may also stem from problems with absorption or metabolism. Food folates are predominantly in polyglutamate form and must be split into monoglutamates for absorption, a conversion that is inhibited by acidic foods and substances found in beans and other legumes. Some drugs, such as phenytoin (dilantin), also interfere with folate absorption, whereas others, such as methotrexate, inhibit folate metabolism. lesions iss I inflammatory Malabsorptive disorders, such as celiac disease and tropical sprue. folates - -> - - - 250 611S Pathogenesis: The metabolism and functions of folate are complex. Here it is sufficient to note that its conversion within cells from dihydrofolate to tetrahydrofolate by dihydrofolate reductase is particularly important. Tetrahydrofolate acts as an acceptor and donor of one-carbon units in ↓ several reactions that are required for the synthesis of deoxythymidine monophosphate (dTMP). If intracellular stores of folate fall, insufficient dTMP is synthesized and DNA replication is blocked, leading to megaloblastic anemia form ofit. 19 absorable  Clinical Features: Insidious, nonspecific symptoms such as weakness and easy " fatigability. May be complicated by the coexistent deficiency of other vitamins, -S especially in alcoholics. - Sore tongue. Diagnosis: serum and red cell folate.  Vitamin B12 (Cobalamin) Deficiency Anemia: B12 is It is stored in the liver in large amount. Food or synthesized by gut flora. Pathogenesis: 1.Peptic digestion releases dietary vitamin B12, allowing it to bind a salivary protein called haptocorrin. 2.On entering the duodenum, haptocorrin–B12 complexes are processed by pancreatic proteases; this releases B12, which attaches to intrinsic factor secreted from the parietal cells of the gastric fundic mucosa. 3.The intrinsic factor–B12 complexes pass to the distal ileum and attach to cubilin, a receptor for intrinsic factor, and are taken up into enterocytes. 4.The absorbed vitamin B12 is transferred across the basolateral membranes of enterocytes to plasma transcobalamin, which delivers vitamin B12 to the liver and other cells of the body.  Pathogenesis: Abnormalities that interferes with vitamin B12 absorption: The most frequent cause vitamin B12 deficiency is pernicious anemia, autoimmune attack on the gastric mucosa that suppresses the production of intrinsic factor. 8"s Chronic atrophic gastritis. sesi Di S195, e - Si Gastrectomy, ileal resection, and disorders that disrupt the function of the 15. distal ileum (such as Crohn disease, tropical sprue, and Whipple disease). i Older persons, gastric atrophy and achlorhydria. so Neurologic lesions: demyelination of the posterior and lateral columns of the spinal cord, sometimes beginning in the peripheral nerves. Bl2def.(1 sos Vitamin B12 is required for recycling tetrahydrofolate, so ????!!!! I B9def.C  Clinical Features: Nonspecific. Mild jaundice, a beefy red tongue. Symmetric numbness, tingling, and burning in the feet or hands, unsteadiness of gait and loss of position sense. Pernicious anemia: increased risk of gastric carcinoma. Diagnosis: (1) low serum vitamin B12 levels, (2) normal or elevated serum folate levels, (3) moderate to severe macrocytic anemia, (4) S leukopenia with hypersegmented granulocytes, and (5) a dramatic ess. I reticulocytic response (within 2 to 3 days) to parenteral administration of L vitamin B12. senting ss.**B Pernicious anemia: serum antibodies to intrinsic factor ↓Wies  E Anemia of Chronic - Its Inflammation: The most common form of anemia in hospitalized patients. Suppression of erythropoiesis by systemic inflammation. 1. Chronic microbial infections, such as osteomyelitis, bacterial endocarditis, and lung abscess 2. Chronic immune disorders, such as rheumatoid arthritis and regional enteritis 3. Neoplasms, such as Hodgkin lymphoma and carcinomas of the lung and breast Pathogenesis: high levels of plasma hepcidin and blunting of erythropoietin synthesis. Clinical Features. As in anemia of iron deficiency. Treatment: treat the underlying condition.  Aplastic Anemia: Multipotent myeloid stem cells are suppressed, leading to bone marrow failure and pancytopenia. Pathogenesis: extrinsic, immune-mediated suppression of marrow progenitors, and an intrinsic abnormality of stem cells.  Clinical Features: All ages and both sexes. shortness of breath Insidious development of weakness, pallor, and dyspnea. platelet ↓ Thrombocytopenia often manifests with petechiae and ecchymoses. abnormal -;s?-I- $19s19E. I Neutropenia may set the stage for serious infections. No splenomegaly. -> RBCs spleens?Siss Hematopoietic stem cell transplantation or immunosuppressive therapy.  Jogis issues - jjj &. 31; wBC, s & Myelophthisic Anemia: Extensive infiltration of the marrow by tumors or other lesions. BMS Metastatic breast, lung, or prostateDylipids)? SBM cancer. Sig - ' & Se II lipids Advanced tuberculosis, lipid storage disorders, and osteosclerosis. Anemia and thrombocytopenia. Immature granulocytic and erythrocytic precursors also may be present (leukoerythroblastosis) along with mild leukocytosis. Treatment is directed at the underlying condition.  HEMOLYTIC ANEMIA A diverse group of disorders with accelerated red cell destruction (hemolysis). Low tissue O2 levels >>> increased erythropoietin >>> growth of erythroid elements and increased release of reticulocytes from the bone marrow. Erythroid hyperplasia and reticulocytosis are hallmarks of all hemolytic anemias. Severe hemolytic anemias >>> extramedullary hematopoiesis appears in the liver, spleen, and lymph nodes. Intrinsic (intracorpuscular) or extrinsic (extracorpuscular). RBC, 91555 (91 Blood vessel s1 19. & hemolysis Ss is & : intravascular spleen S1 extravascular.."  Hemolytic Anemia: Intravascular hemolysis: within the Extravascular hemolysis: circulation. destruction of red cells by Mechanical forces, biochemical or phagocytes in spleen). physical agents that severely Hyperbilirubinemia and jaundice, damage the red cell membrane. &,5 stemming from degradation of Hemoglobinemia, hemoglobinuria, hemoglobin in macrophages and hemosiderinuria. Varying degrees of splenomegaly. Loss of iron. Bilirubin-rich gallstones (pigment Decreased serum levels of stones) and an increased risk of haptoglobin. cholelithiasis. -  Hereditary Spherocytosis Inherited defects in the red cell membrane skeleton that lead to the formation of spherocytes. Autosomal dominant trait. Surface area-to-volume ratio decreases. Hereditary Spherocytosis: st commentation  Morpholog y On smears: spherocytes are dark red and lack central pallor. Erythroid hyperplasia. Reticulocytosis. Splenomegaly is more common and prominent in hereditary spherocytosis than in any other form of hemolytic anemia. Cholelithiasis. /138 Hereditary Spherocytosis  Clinical Features: Anemia, splenomegaly, and jaundice. Increased osmotic fragility: can help establish the diagnosis. * Aplastic crises, the most severe of which are triggered by parvovirus B19 infection/ Blood transfusions. No specific treatment. M -I Splenectomy improves the anemia. capsulated) - bacteria - &  glucose-6-phosphate dehydrogenase (G6PD) deficiency: Endogenous and exogenous oxidants, which are normally inactivated by reduced glutathione (GSH). Abnormalities affecting enzymes responsible for the synthesis of GSH leave red cells vulnerable to oxidative injury and hemolysis. The G6PD gene is on the X chromosome. Episodes of intravascular hemolysis. Exposure to an environmental factor: 1. Incriminated drugs include antimalarials (e.g., primaquine), sulfonamides, nitrofurantoin, phenacetin, aspirin (in large doses), and vitamin K derivatives. 2. Infections. materials ↑ 3. Certain food. I 2 Heinz bodies: Oxidized hemoglobin denatures and precipitates. Bite cells.  Clinical Features: Hemolysis typically develops 2 or 3 days after drug exposure and is of variable severity. ·Dis ↑ 1. G6PD A−: approximately 10% of black males in the United States Normal enzymatic activity but a decreased half-life, older G6PD A− red cells become progressively deficient in enzyme activity and GSH. 2. G6PD Mediterranean, found mainly in the Middle East, the enzyme deficiency and the hemolysis that occur on exposure to oxidants are more severe.