Lecture 11 CH13 Hematopoietic and Lymphatic Systems.pptx.pdf

The Hematopoietic and Lymphatic Systems Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives Describe the composition of the blood and explain the function of each component. Explain the functions of the lymphatic system. 2. Outli...

The Hematopoietic and Lymphatic Systems Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives Describe the composition of the blood and explain the function of each component. Explain the functions of the lymphatic system. 2. Outline the process whereby blood cells are produced. 3. Describe the structure and function of hemoglobin. 4. List the usual causes of anemia as a result of bone marrow damage and anemia caused by accelerated blood destruction. Explain their treatment. 5. List and describe the inheritance and effects of abnormal hemoglobin, such as sickle cell disease and thalassemia. 6. Describe the causes and effects of polycythemia and thrombocytopenia. 7. Explain the role of the spleen in protecting the body against infection. Describe the effects of a splenectomy on the body’s defenses, and relate them to the management of a patient who has had a splenectomy. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 1. Learning Objectives Describe the cause and clinical manifestations of infectious mononucleosis. 9. Describe the types and causes of leukemia; describe the precursors of leukemia. 10. Compare and contrast leukemia and lymphoma. 11. List the common causes of lymph node enlargement. 12. Describe the process and problems involved in hematopoietic stem cell therapy. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 8. Composition and Function of Human Blood Volume of blood: About 5-6L, but varies according to size of individual Almost half of blood consists of cellular elements suspended in plasma (viscous fluid) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Blood transports substances to tissues via circulatory system: ▪ Plasma – fluid component of blood ▪ Oxygen, nutrients, hormones, leukocytes, red cells, platelets, antibodies ▪ Albumin (oncotic pressure), Antibodies (immunity) ▪ Carbon dioxide and other waste products of cell metabolism to the excretory organs of the body Cellular Elements of Human Blood ↓ stopping of blood flow Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Cellular elements ▪ Red blood cells – Oxygen/Carbon Dioxide exchange ▪ Leukocytes (WBC) – Immune functions ▪ Neutrophils – most numerous – first line ▪ Monocytes – phagocytic Macrophages ▪ Eosinophils – allergy, parasitic infections ▪ Lymphocytes – adaptive immunity ▪ Basophils – parasitic infections ▪ Platelets - hemostasis Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Stem cells: Precursor cells in bone marrow that differentiate to form red cells, white cells, and platelets Red Cells and Leukocytes Leukocytes ▪ Less numerous ▪ Different types ▪ Survival from several hours to several years ▪ Ganulocytes/ Polymorphpnucleargraulocytes (PMN - Eosinophils, Basophils, Neutrophils) ▪ Some lymphocytes produced in the bone marrow, but mainly found in lymph nodes and spleen Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Red Blood cells (RBC) ▪ Primarily concerned with transport of oxygen ▪ Biconcave disc – large sa:volume ratio ▪ Most numerous cells in blood ▪ Survive 4 months (120 days) ▪ Erythroblast: Precursor cell in bone marrow ▪ Hemoglobin: Oxygen-carrying protein formed by the developing red cell Leukocytes Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Types of leukocytes ▪ Neutrophils ▪ Most numerous in adults ▪ Make up 60-70% of total circulating WBC ▪ Actively phagocytic ▪ Predominant in inflammatory reactions ▪ First line of defense - vital ▪ Monocytes (3-5%) ▪ Increased in certain types of chronic infection ▪ Circulate to sites of inflammation ▪ Transition to Macrophages (APC) ▪ Infection/tissue repair Lymphocytes Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Types of leukocytes, cont. ▪ Eosinophils/Basophils ▪ Increased in allergic reactions ▪ Increased in presence of animal–parasite infections ▪ Present in low numbers (lowest) Lymphocytes (15-20%) ▪ Next most common leukocytes in adults (B/T cells) ▪ Predominant leukocytes in children ▪ Small fraction in circulation (LN) ▪ Mostly located in lymph nodes, spleen, lymphoid tissues ▪ Also traffic though lymphatic system ▪ Take part in cell-mediated and humoral defense reactions Platelets ▪Much smaller than leukocytes ▪Represent bits of the cytoplasm of megakaryocytes, the largest precursor cells in bone marrow ▪Short survival, about 10 days Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪Essential for blood coagulation Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Normal RBC Hematopoiesis Hematopoiesis: Formation and development of blood cells ▪ Substances necessary for hematopoiesis ▪ Protein ▪ Folic Acid, Vitamin B12 (required for DNA synthesis ▪ Iron Decreased RBC production if any of these are lacking Regulated by oxygen content in blood – stimulates hormone (epo) release from kidneys Proerythroblasts in bone marrow mature into reticulocytes -lose nucleus and Hg synthesis+++++ -Reticulocytes (large, DNA/RNA present) leave bone marrow and differentiate into RBC in circulation. -High reticulocyte count indicates body is creating a lot of RBC Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Bone marrow replenishes blood cells (damage/age) Normal Hematopoiesis ▪White cell production: regulated by Interleukin levels/ response to infection – complex ▪RBC derive energy from enzymatic breakdown of glucose (anaerobic glycolysis) because they don’t have mitochondria No nucleus, so enzymes can’t be replaced –activity gradually declines over 4 months Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪Red cell production: Regulated by oxygen content of the arterial blood – stimulated by erythropoietin Hemoglobin ▪ 96% of RBC content ▪ Heme: Porphyrin ring that contains an iron atom ▪ Globin: Largest part of hemoglobin; forms different chains designated by Greek letters such as alpha, beta, gamma, delta, and epsilon ▪ Most common in adults 98% – HgbA (2-alpha, 2-beta s.u.) ▪ Porphyrin ring: Produced by the mitochondria; iron inserted to form heme Hemoglobin delta is rare (1%) • not sure what it does • may elevate when there is damage to beta hemoglobin to compensate Difference between fetal development and once we are born • any mutations and damage to alpha hemoglobin will be severe • beta is replaced by gamma in fetal development • beta ramps up after birth In sickle cell anemia, gamma is elevated to compensate for alpha loss Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Hemoglobin: Tetramer composed of four subunits, each one consisting of heme and globin Red Cells and Hemoglobin Since they have a bit of DNA ▪ Once they exit the bone marrow, in 24-48 hours, reticulocyte matures and survives in the circulation for about 4 months (RBC) ▪ Globin chains: Produced by ribosomes; joined to heme to form a hemoglobin unit ▪ Four subunits aggregate to form the complete hemoglobin tetramer Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Reticulocyte: Young red cell without a nucleus, but retains some organelles; identified by special strains Red Cell Life Cycle damaged and poorly shaped ▪ Hemoglobin degraded and excreted as bile by liver ▪ Porphyrin ring cannot be salvaged ▪ Globin chains break down and are used to make other proteins ▪ Iron extracted and saved to make new hemoglobin Conserved - when broken down it produces bilirubin - when too much is destroyed it builds up and we see it as jaundice not excreted by our body very easily (no natural mechanism for this) - most commonly recycled Red cell production regulated by oxygen content of arterial blood ▪ Reduced oxygen supply stimulates erythropoiesis ▪ Reduced oxygen tension does not act directly on bone marrow; mediated by the kidneys, which produce erythropoietin Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Worn out red cells removed in the spleen Oxygen Transport by Hemoglobin Oxygen Pulling in carbon dioxide Methemoglobin iron (Fe 3+) not in ferrous state – can’t bind oxygen, inherited disorder or response to toxic agents (trace amounts present spontaneously) also occurs naturally in the body all the time but tends to convert back with enzymes in our body ▪ Several drugs/chemicals that can oxidize hemoglobin to methemoglobin (chem - Nitrates, chlorobenzene, drugs – benzocaine, chloroquine, amyl nitrate). Tx: oxygen therapy, ascorbic acid (reduces oxidation), methylene blue (reverses), transfusion Carboxyhemoglobin – Binds CO with high affinity (200x stronger than oxygen), blocks oxygen binding, products of incomplete combustion. Tx. Hyperbaric oxygen therapy (pure oxygen 2-3X atm pressure) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Hemoglobin is unique in its ability to enter into reversible combination with oxygen ▪ Must be in its ferrous form (Fe 2+) to bind/ release oxygen ▪ High partial pressure oxygen in lungs – promotes binding ▪ Low partial pressure oxygen in tissues – promotes release Iron metabolism Very closed loop - no effective uptake/excretion of iron / ▪ No mechanism for iron elimination in body – blood loss ▪ Duodenal cells produce Hepcidin to block iron uptake by duodenal cells, interferes with iron transport But does not remove it ▪ Hepcidin levels are decreased/increased in response to iron stores can be stimulated in inflammatory conditions Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Iron reserves stored in liver, bone marrow spleen Hemochromatosis ▪ Common genetic disease transmitted as autosomal recessive trait – chronically absorb too much iron ▪ Iron overload due to inability to reduce iron levels ▪ Iron accumulation leads to organ damage followed by scarring and permanent derangement of organ function ▪ Manifestations of disease take years to develop ▪ Tan to brown skin ▪ Diabetes ▪ Cirrhosis (liver damage) ▪ Heart failure ▪ Blood test (evaluated serum iron/ ferritin) CT scan shows increased iron deposit in heart liver and kidneys ▪ Treatment: Periodic removal of blood (phlebotomy) until iron stores are depleted, and use of iron chelation treatment to remove iron Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Overload can also happen in patients who take iron supplements chronically, or have blood disorders where there is lost of RBC destruction (sickle cell) Can cause fetal toxicity for pregnant women Anemia Causes Reduction in red blood cells or subnormal level of hemoglobin Can have anemia because you are not producing enough RBC or they are being destroyed too quickly ▪ Insufficient raw materials ▪ Iron deficiency ▪ Vitamin B12 deficiency ▪ Folic acid deficiency ▪ Inability to deliver adequate red cells into circulation due to marrow damage or destruction (aplastic anemia); replacement of marrow by foreign or abnormal cells (Cancer - takes away folic acid from RBC) Excessive loss of red cells ▪ External blood loss (hemorrhage) ▪ Shortened survival of red cells in circulation (sickle cell, thalassemia) ▪ Defective red cells: Hereditary hemolytic anemia ▪ Accelerated destruction of cells from anti-RBC antibodies or from mechanical trauma to circulating red cells Instead of lasting 4 moths, they may last days because they are misshaped or damaged Autoimmune causes - body creates antibodies against RBC and destroys them Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Inadequate production of red cells Classification of Anemia Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Anemia: Morphologic Classification This could be from blood loss problem with nutrient supply Problem with hemoglobin production paler and not as red as a normal RBC ▪ Hypochromic microcytic anemia: Smaller than normal and reduced hemoglobin content Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Classification based on red cell appearance suggests the etiology of the anemia ▪ Normocytic anemia: Normal size and appearance ▪ Macrocytic anemia: Cells larger than normal impaired ▪ Folic acid deficiency ▪ Vitamin B12 deficiency ▪ Microcytic anemia - smaller cells (thalassemia) ▪ Hypochromic anemia: Reduced hemoglobin content Iron-Deficiency Anemia Most common type of anemia ▪ Iron absorbed from duodenum, transferred via transferrin, stored as ferritin Pathogenesis ▪ Inadequate iron intake in diet ▪ Infants during periods of rapid growth ▪ Adolescents subsisting on inadequate diet ▪ Inadequate reutilization of iron present in red cells due to chronic blood loss ▪ Chronic infection/inflammation, cancers (increased Il-6 production increases hepcidin production –blocks iron uptake) - Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Hypochromic microcytic anemia (not enough iron) Iron-Deficiency Anemia ▪ Serum ferritin (low) ▪ Serum iron (low) ▪ Serum iron-binding capacity (high) Lots of availability for binding of ferritin - shows problems with amount of iron available Characteristic laboratory profile ▪ Low serum ferritin and serum iron ▪ Higher than normal serum iron-binding protein ▪ Lower than normal percentage iron saturation Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Laboratory tests in blood Iron-Deficiency Anemia Need to find cause and treat it as this alone is not enough Examples ▪ Infant with a history of poor diet ▪ Adults: Common cause is chronic blood loss from gastrointestinal tract (bleeding ulcer, ulcerated colon carcinoma) ▪ Women: Excessive menstrual blood loss ▪ Too-frequent blood donations ▪ Chronic disease - tx Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Treatment ▪ Primary focus: Learn cause of anemia ▪ Direct treatment toward cause rather than symptoms ▪ Administer supplementary iron Vitamin B12 Deficiency Anemia Vitamin B12: Meat, milk, and foods rich in animal protein – risk for vegetarians more widespread Absence or deficiency of vitamin B12 or folic acid ▪ Abnormal red cell maturation or megaloblastic erythropoiesis with formation of large cells called megaloblasts ▪ Mature red cells are larger than normal or macrocytes; corresponding anemia is called macrocytic anemia ▪ Abnormal development of white cell precursors and megakaryocytes result in Leukopenia (low WBC), thrombocytopenia (low platelets) Tends to be fewer of them Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Folic acid: Green leafy vegetables and animal protein foods ▪ Both required for normal hematopoiesis and normal maturation of many other types of cells ▪ Vitamin B12: For structural and functional integrity of nervous system; deficiency may lead to neurologic disturbances Folic Acid Deficiency Anemia Pathogenesis ▪ Inadequate diet: Encountered frequently in chronic alcoholics ▪ Poor absorption caused by chronic intestinal disease ▪ Occasionally occurs in pregnancy with increased demand for folic acid • Chronic increased RBC production Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com -relatively common, body has very limited stores, which rapidly become depleted if not replenished continually Pernicious Anemia Causes ▪ Gastric mucosal atrophy; also causes lack of secretion of acid and digestive enzymes (aging) ▪ Auto antibodies directed against gastric mucosal cells and intrinsic factor ▪ Surgery to remove sections of stomach (ulcer, gastric bypass, gastric cancer resection) ▪ Chronic intestinal diseases (Crohn’s,IBD) (Most common form of pernicious anemia) • Genetic Some of the enzymes / proteins are not functional or produced properly Treatment - increased oral dose (B12 supplements) or Intramuscular injections Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Lack of intrinsic factor results in macrocytic anemia ▪ Vitamin B12 in food combines with intrinsic factor ▪ Vitamin B12 : intrinsic factor complex absorbed in ileum Bone Marrow Suppression, Damage, or Infiltration no production of RBC or WBC (check) • Idiopathic causes 3 arise spontaneously , reasons unknown Suppression of bone marrow precursors will also effects WBC and platelets – Pancytopenia (anemia, leukopenia, thrombocytopenia) ▪ Marrow infiltrated by tumor or replaced by fibrous tissue Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Conditions that depress bone marrow function ▪ Anemia of chronic disease: Mild suppression of bone marrow function (parvoirus B19) – recovers once infection controlled Aplastic anemia: ▪ Marrow injured by radiation ▪ anticancer drugs or chemicals ▪ Autoantibodies, CTL autoimmunity Bone Marrow Suppression, Damage, or Infiltration ▪ Blood and platelet transfusions (supportive, symptomatic) ▪ Immunosuppressive drugs (if autoimmune cause) ▪ Hemopoietic stem cell transplant in highly selected cases of aplastic anemia (cord blood, bone marrow, peripheral stem cells) ▪ In many cases, there is no specific treatment Platelets, clotting factors, etc. symptomatic or replying on BM transplant Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Treatment depends on cause Accelerated Blood Destruction RBC last about 4 months – defects in RBC or damage will have them targeted of r destruction in the spleen prematurely (sickle cell, thalassemia -hereditary) Can also be autoimmune Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Result of either an intrinsic defect in red cell structure or an extrinsic condition that shortens circulating life of red cell Hereditary Hemolytic Anemia -round ▪Abnormal shape: Hereditary spherocytosis Instead of biconcave disc, damage to cytoskeleton creates a disk • not good for going thru thin capillaries, weaker and susceptible to more damage so they will not survive as long ▪Abnormal hemoglobin: Hemoglobin S (sickle hemoglobin); hemoglobin C; both found predominantly in persons of African descent ▪Defective hemoglobin synthesis: Thalassemia minor and major; globin chains are normal, but synthesis is defective (south east asia, Greek and Italian ancestry) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Hereditary hemolytic anemia: Genetic abnormality prevents normal survival Hereditary Hemolytic Anemias Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Hereditary Spherocytosis Mutration defect in cytoskeleton protein - fail to form bi-concave disk shape smaller surface area:size fragile increased destruction by spleen moderate/mild anemia TX. Transfusion, B12, spleenectomy Also seen in autoimmune hemolytic anemias FIGURE 13-5 A stained blood film from a person with hereditary spherocytosis. The many small dark cells with little or no central pallor are spherocytes (arrows). The larger, more normal-appearing red cells are young red cells that have the same cell membrane defect but have not been circulating long enough to acquire a spherical shape. The relative large, faintly blue-staining red cell in the center of the field is a reticulocyte. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com • • • • • Thalassemia Defective synthesis of alpha or beta globulin - stiff /malformed ▪ Lack of Alpha and Excess beta chains form unstable Beta tetramers (defective oxygen exchange) ▪ With disease you get microcytic, hemolytic anemia – may require repeated transfusions throughout life • iron overload risk, BMT at risk of iron overload • important for these patients to do exchange transfusion Forms Beta globulin Hgb ▪ Beta – (2 genes) Heterozygous-mild, homo - severe overproduction of Alpha chains precipitates in RBC and shortens survival (chronic anemia) -hypochromic, microcytic anemia -iron overload risk Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Alpha – (4 genes) 1- no change 2 -trait with mild disease, 3 severe disease, 4 – incompatible with life (hydrops fetalis) Sickle cell Hemoglobin S (beta Hgb point mutation) ▪ In deoxygenated conditions – HgbS form rigid fibers causing “sickling”, reversible Constant sickling wears out cells and sickled cells are targeted for early destruction by the spleen Cells are also sticky and can form blockages in blood vessels One mutation Sickle cell trait – heterozygous, generally asymptomatic Sickle cell disease – homozygous, chronic health problems also lung - ACS (acute chest syndrome) Vaso-occlusive crisis – severe, abdominal pain (kidney, liver spleen infarction) ... Chronic bone (occlusion in bone marrow), joint pain – with anemia Splenic sequestration crisis Chronic disease, gets worse as patient ages can replace fetal hemoglobin Significant factor in managing and controlling disease Tx — RBC transfusion, hydroxy urea, BMT, pain control • Gene therapy trials promising - point mutation betaH hard to get good BMT match since it runs in families Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Present in areas where Malaria is/was common Distortion of red cells FIGURE 13-6 Distortion of red cells containing sickle hemoglobin when incubated under reduced oxygen tension. (A) Overview of cells under low magnification (×100). (B) Higher magnification view of red cell distortion caused by sickle hemoglobin. Courtesy of Leonard V. Crowley, MD, Century College. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com In deoxygenated state, it forms (check) Acquired Hemolytic Anemia Normal red cells that are unable to survive due to a hostile environment Autoimmune reaction ▪ Destruction of red cells by mechanical trauma Pass through enlarged spleen (splenomegaly) causes damage. because of clots and liver damage Damaged by contact with some part of artificial heart valve Clotting Disorders: Disseminated intravascular Coagulation (DIC), Thrombotic Thrombocytopenic Purpura TTP –clots form in small blood vessels damaging RBC. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Attacked and destroyed by antibodies Diagnostic Evaluation of Anemia ▪ History and physical examination Iron, ferritin, iron binding capacity, RBC size (MCV)/Varibaility (MCHC), hemoglobin levels ▪ Complete blood count to assess degree of anemia, leukopenia, and thrombocytopenia ▪ Blood smear to determine if normocytic, macrocytic, or hypochromic microcytic To see if you can see sickling, etc. ▪ Reticulocyte count to assess rate of production of new red cells ▪ Lab tests to determine iron, B12, folic acid levels ▪ Bone marrow study to study characteristic abnormalities in marrow cells ▪ Evaluation of blood loss from gastrointestinal tract to localize site of bleeding Also CT scans for iron accumulation biopsy to see if there are problems in development there Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com • Polycythemia Secondary polycythemia (common) areas of higher elevation Kidneys will try to stimulate more RBC production to compensate chronic infection/inflammation Primary or polycythemia vera (rare) ▪ Manifestation of diffuse marrow hyperplasia of unknown etiology ▪ Overproduction of red cells, white cells, and platelets ▪ Some cases evolve into granulocytic leukemia Could be sign of early leukemias In rare cases Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Reduced arterial oxygen saturation leads to compensatory increase in red blood cells (increased erythropoietin production) ▪ Emphysema, pulmonary fibrosis, congenital heart disease, increased erythropoietin production by renal tumor, splenectomy/liver disease Polycythemia Complications and Treatment ▪ Clot formation due to increased blood viscosity and platelet count Treatment ▪ Primary polycythemia: Treated with drugs that suppress marrow function ▪ Secondary polycythemia: Periodic removal of excess blood • treat cause Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Complications Thrombocytopenia Primary/ Immune thrombocytopenic purpura (ITP) ▪ Associated with platelet antibodies ▪ Bone marrow produces platelets, but they are rapidly destroyed ▪ First encountered in children (generally after viral infection) and subsides spontaneously after a short time ▪ Tends to be chronic in adults ▪ Tx with corticosteroids if required (immune suppression) or spelenctomy Good chance they grow out of it - peripheral tolerance life-long problem Also IVIG - flood the body with all sorts of antibodies to interfere with macrophages (won’t have enough MC) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Secondary thrombocytopenic purpura ▪ Damage to bone marrow from drugs or chemicals ▪ Bone marrow infiltrated by leukemic cells or metastatic carcinoma ▪ Can be caused in later stages of leukemia (particularly in CLL) Lymphatic System Also provides return of lost circulatory volume to vascular system Structure ▪ Lymph nodes: Bean-shaped structures consisting of a mass of lymphocytes supported by a meshwork of reticular fibers that contain scattered phagocytic cells ▪ As lymph flows through the nodes, phagocytic cells filter out and destroy microorganisms and foreign matter ▪ Clustered where lymph channels are located Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Primary function: Provide immunologic defenses against foreign material via cell-mediated and humoral defense mechanisms Lymphatic System Thymus: Overlies base of heart; large during infancy and childhood; undergoes atrophy in adolescence ▪ Essential in prenatal development of lymphoid system and in formation of body’s immunologic defense mechanisms ( T cell development/ selection Spleen: Specialized to filter blood ▪ Compact mass of lymphocytes and network of sinusoids (capillaries with wide lumens) ▪ Macrophages (phagocytosis) ▪ For antibody formation – pathogen elimination and phagocytosis of senescent red cells ▪ Detection and Removal of pathogens in blood ▪ Immune cells can exit to lymphatic system, but not enter Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Lymphoid tissue: Present in thymus, tonsils, adenoids, lymphoid aggregates in intestinal mucosa, respiratory tract, and bone marrow Splenectomy Reasons for splenectomy ▪ Traumatic injury: To prevent fatal hemorrhage ▪ Blood diseases: Excessive destruction of blood cells in the spleen (hereditary hemolytic anemia) ▪ Prevent chronic splenomegaly Cancer – Leukemia, Lymphoma commonly pulled out in response to disease due to complications Very common and will be much more susceptible to them wont be as strong or effective especially the immune functions Wouldn’t do spleen transplant because it is a massive lymph node but removal is not that bad - transplant - immune suppression, etc. • risk-reward is not worth it Treatment: vaccines, antibiotic prophylaxis Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Effects ▪ Less-efficient elimination of bacteria (especially if blood borne) ▪ Impaired production of antibodies ▪ Predisposed to systemic infections ▪ In particular, patients are at risk from Streptococcus pneumoniae, Haemophilus influenzae, and meningococcus infections ▪ Risk of increased platelet /RBC (due to inefficient clearance/removal) – pro-coagulatory Role is taken over by liver/secondary spleen (30% of people) Lymphatic System Diseases Children/adults in chronic infection cases (teens - puberty —> develop mononucleosis) Risks ▪ Avoid body contact sports until spleen is no longer enlarged to avoid risk of splenic rupture ▪ Persons with compromised immune system, unrestrained B cell proliferation may give rise to B cell lymphoma If you do get mononucleosis spleen will be enlarged Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Infectious mononucleosis: usually caused by Epstein-Barr virus (EBV-bcell 90%) or CMV – Tcell/macrophages (5-7%) ▪ EBV Infection of B lymphocytes causes diffuse lymphoid hyperplasia of spleen, lymph nodes, lymphoid tissues ▪ Fever, sore throat, fatigue ▪ Cytotoxic (CD8+) lymphocytes and antibodies produced by plasma cells destroy most of infected B cells ▪ Characterized by enlarged and tender lymph nodes ▪ Mostly encountered by young adults; transmitted by close contact, “kissing disease” ▪ Disease is self limiting but can take months to recover Lymphatic System Diseases Enlarged LN ▪ Result from a metastatic tumor in node ▪ Early manifestation of leukemia or malignant lymphoma Spread of Neoplasms ▪ Metastatic tumors: Breasts, lung, colon, other sites ▪ Nodes first affected lie in immediate drainage area of tumor ▪ Tumor spreads to more distant lymph nodes through lymphatic channels Can get stuck on lymph nodes and grow there and disrupt lymph node tissue Malignant lymphoma ▪ Hodgkin lymphoma ▪ Non-Hodgkin lymphoma faster forming Slower and better prognosis ▪ Lymphocytic leukemia: From lymphoid precursor cells; acute (primitive forms) or chronic (mature cells) moee centered ion bome marrow and spills over to the blood stream Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Manifestation of localized or systemic infection Leukemia A neoplasm (Cancer) of hematopoietic tissue Doesn’t destroy the production but all the function of the immune system • forms from one type of cell ▪ Cells may be mostly mature or extremely primitive ▪ Overproduction of white cells demonstrated in the peripheral blood by a very high white blood count ▪ Aleukemic leukemia: Condition in which white cells are confined to the bone marrow such that their number in the peripheral blood is normal or decreased Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Leukemic cells diffusely infiltrate the bone marrow and lymphoid tissues, spill over into the bloodstream, and infiltrate throughout various organs of the body Myelodysplasia (Preleukemia) Recently grouped together under the general term myelodysplastic syndrome In general, the more severe the maturation disturbance in the bone marrow, the greater the likelihood that leukemia will occur Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com A disturbed growth and maturation of marrow cells ▪ Anemia: Reduced number of erythrocytes ▪ Leukopenia: Reduced number white cells ▪ Thrombocytopenia: Reduced number of platelets Although it is called preleukemia, not all patients develop leukemia Leukemia: Classification Basis for classification of leukemia ▪ Cell type ▪ Granulocytic, lymphocytic(lymphoid), monocytic (myeloid) ▪ Maturity of leukemic cells ▪ Acute if immature cells (early precursor) ▪ ALL-children, CML, CLL, AML adults ▪ Chronic if mature cells best prognosis CLL(chronic lymphocytic leukemia, CML chronic myelogenous leukemia, ALL acute lymphocytic leukemia, AML (acute myeloid leukemia) Worse for prognosis and probably the most danger Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Any type of hematopoietic cells can give rise to a leukemia, but the most common types are: ▪ Granulocytic ▪ Lymphocytic ▪ Monocytic Leukemia: Clinical Features Leukemic cells crowd out normal cells causing ▪ Anemia: Inadequate red cell production ▪ Thrombocytopenia: Causes bleeding ▪ Infections from inadequate number of normal white cells Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Manifestations caused by impairment of bone marrow function Lots of fat globules present in bone marrow Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Pretty much all the same cell type and destroyed fat sites Leukemia: Clinical Features Chronic leukemia: Evolution of disease proceeds at a relatively slow pace and often can be controlled Acute leukemia: A rapidly progressive disease, more difficult to control characterize cells Diagnosis – flowcytometry (phenotyping) bone marrow biopsy, Karyotyping (numbers, disease specific risk genes – BCR/ABL fusion) Most dangerous cancers are the ones that have normal karotype • best prognosis - severely disturbed karyotype Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Caused by infiltration of organs by leukemic cells causing ▪ Splenomegaly: Enlarged spleen ▪ Hepatomegaly: Enlarged liver ▪ Lymphadenopathy: Enlarged lymph nodes ▪ Bone pain – expansion of cells in bone marrow Lymphoma When cancerous cells form solid tumors in LN Disrupts immune function Classification: Hodgkin/Non-Hodgkin Hodgkin – young adults, starts in single LN and spreads to others and eventually other parts of the body. Usually detected early as a single or group of enlarged LN For Hodgkin Reed- Steinberg cells (large atypical B-cells) that act as nucleus of tumor and secrete cytokines to attract other tumor cells Non-Hodgkin – older adults, variable in appearance an progression, often not detected until widespread dissemination has occurred Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Disease of Lymphocytes: Most are B cell (80%) or T cells Treatment of Leukemia and Lymphoma ▪ Destruction of malignant cells by chemotherapy or radiation to produce remission ▪ Treat relapses surgical options aren’t there as you can’t resect B or T cell Hematopoietic Stem Cell Therapy (BMT, peripheral, cord blood) ▪ Replacement of malignant cells by hematopoietic stem cells from peripheral blood or bone marrow ▪ Autologous (self) allogeneic (not self) ▪ Deal with problem of rejection by donor matching or drug treatment (GVH) – want closest match possible (HLA testing – 6 antigen match) ▪ High risk procedure and lifetime immune suppression 50% 5y survival rate with good sibling match – lower if unrelated match Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 3 Phases: Induction/Consolidation/Maintenance