Chapter 9: Hematopoietic & Lymphoid Systems

Aplastic Anemia

-2 Forms- Idiopathic and Secondary -Bone Marrow depleted of Hematopoetic cells- consists only of Fibroblasts, fat cells and scattered Lymphocytes Symptoms- Uncontrollable Infxn, bleeding tendency, chronic fatigue, weakness

Burkitts Lymphoma

-Highly malignant tumor composed of small B cells -prominent extranodal masses more prominent than enlarged lymph nodes

Clotting Factor I

Fibrinogen

Iron Deficiency Anemia- Cell Morphology

Hypochromic Microcytic Anemia

Granulocytosis

Increase in neutrophilic granuloctyes -Pyogenic Bacterial infxns

Macrocytic Cell Size

Megaloblastic Anemia

B12 Deficiency

Pernicuous Anemia Lack of gastric intrinsic Factor Diagnosis: Schilling Test

Composition of Blood

Plasma (55%) - H2O- 92% + Protein- 7% Cells (45%)- RBC-45% + Leukocytes + Thrombocytes

Sickle Cell Anemia

Substitution of Glutamic Acid by Valine Synthesis of abnormal chain of globin

Symptoms Multiple Myeloma

hypercalcemia, renal failure, anemia, leukopenia

Folic Acid Deficiency

inadequate intake malabsorpiton because of intestinal disease

Polycythemia Type 1

Clonal proliferation of hematopoetic stem cells (polycythemia Vera) Uncontrolled production of RBC and increase in total RBC mass

Acute Myelogenous Leukemia (AML)

-Most common form in Adults -clonal proliferation off myeloblasts in bone marrow (20% myeloblasts) -without treatment die within 6 months of symptoms

Acute Lymphoblastic Leukemia (ALL)

-Most common in children -massive infiltration of bone marrow and peripheral blood with immature lymphoid cells (blasts) -recurrent infxns. weakness, bleeding into skin and organs

Multiple myeloma pathogenesis

-malignant plasma cells proliferate in bone marrow and destroy surrounding bone -punched out holes (lytic lesions) in skulls, ribs, vertebrae

Diffuse large cell lymphoma

-most aggressive form -tissue is infiltrated with large lymphoid cells with irregular nuclear outlines and prominent nucleolus

Follicular Lymphoma

-t(14:18) results in activation of blc-2 -most common -seen in older people and slow growing

Different Types of Anemia (4)

1.) Aplastic Anemia 2.) Fe2+ Deficiency Anemia 3.) Megaloblastic Anemia 4.) Hemolytic Anemia- Sickle Cell Anemia, Thallasemia, AI Hemolytic Anemia

Non- Hodgkin Lymphoma types (3)

1.) Follicular 2.) Diffuse Large Cell 3.) Burkitts

Hodgkin Lymphoma Stages

1.) Involvement of single lymph node or group of nodes 2.)Involvement of 2 or more site on same side of diaphragm 3.)Disease on both sides of diaphragm; may include spleen or extranodal 4.)Widespread extralymphatic involvement (Liver, bone marrow, lung, skin)

Sickle Cell Anemia Pathogenesis

@ Low oxygen partial pressures (venous) abnormal HbS molecules crystallize into long insoluble polymerized rods resulting in occlusion of capillaries compromising oxygen delivery to tissues -multiple infarcts in various organs

Types of Leukemia (4)

Acute Lymphoblastic Leukemia (ALL) Acute Myelogenous Luekumia (AML) Chronic Myelogenous Leukemia (CML) Chronic Lymphocytic Leukemia (CLL)

Morphology of Anemia

CELL SIZE - Normocytic(Normal) -Macrocyctic(Large) -Microcytic (Small) DEGREE OF HEMOGLOBINIIZATION -Normochromic (Normal) -Hypochromic (Pale)

Blood Coagulation

Ca2+ binds TPA TPA cleaves prothrombin into thrombin Thrombin + Ca2 converts Fibrinogen into Fibrin

Clotting Factor IV

Calcium

Globin

Chains produced by ribosomes and are joined to heme. Chains alpha, beta, gamma, delta, epsilon alpha and beta= Hg A- most common in adults

Phases of Chronic Myelogenous Leukemia

Chronic, Accelerated, Blast Crisis

Hemophilia

Congenital clotting factor defects, sex linked clotting factor deficiency. Uncontrollable bleeding following trauma and subcutaneous hematomas.

Burkitts Lymphoma Types (2)

Endemic variety- sub saharan Africa, children with EBV Sporadic Variety- Children and young adults- abdominal mass (ovarian; intestine)

Polycythemia

Erythocytosis: increased number of red blood cells

Megaloblastic Anemia- Symptoms

Fatigue, SOB, weakness Destruction of posterior and lateral columns in spinal cord -loss of sense of vibration and deep tendon reflexes

Hypochromic Cell

Fe2+ Deficiency Anemia

Microcytic Cell Size

Fe2+ Deficiency Anemia & Thallasemia

Hematopoiesis

Formation of blood cellular components from hematopoietic stem cells

Thalassemia

Genetic defect in synthesis of HbA that reduces the rate of globin chain synthesis- No abnormal Hg Produced Beta Thalassemia- Decreased Beta Chain synthesis (more common) Alpha Thalassemia- Decreased alpha chain synthesis

Normochromic Cell

Hemolytic Anemia

Bleeding Disorders

Hemorrhage- escape of blood from vessels or heart, external, internal -occur as a result of defects - vessel wall related, platelet related or clotting factor related

Polycythemia Symptoms

Hypertension, dark red (flushed) face, headaches, visual problems, neurologic symptoms, splenomegaly (enlarged spleen)

Eosinophillic Leukocytosis

Increase in eosinophils -allergy, skin disease, parasitic

Lymphocytosis

Increase in lymphocytes -chronic infxns (tb), Viral infxns (Hep A, Mono), Pertussis

Leukocytosis-

Increase in number of WBC in peripheral blood enlarged spleen and lymph nodes

Iron Deficient Anemia- Cause

Increase loss of Iron- Chronic Bleeding Inadequate Iron intake or Absorption Increase Iron requirements

Hemolytic anemia

Increased RBC destruction (Hemolysis)

Polycythemia Type 2

Increased RBC volume due to bone marrow hyperplasia by erythopoietin. Caused by prolonged hypoxia and living at high altitudes Anoxia secondary to congenital heart disease and chronic lung disease

Hemolytic Anemia Causes

Intracorpuscular Defects- Structural abnormalities Extracorpuscular Defects- Antibodies, infxs agents, mechanical

Hemoglobin

Iron containing Oxygen transport metalloprotein in RBC. Tetramer 4 Heme groups and 4 Globins

Hemoglobin Synthesis requires

Iron, B12, B6 and Folic Acid

Leukocyte Disorders (3)

Leukopenia Leukocytosis Leukemia

Thalassemia Symptoms

Long distorted bones Facial and cranial bones in characteristic crew cut appearance

Chronic Lymphocytic Leukemia (CLL)

Malignant Disease involving Lymphoid Cells- >50 years -should be expected if # lymphocytes exceeds 5000/ mL

Lymphoma Definition

Malignant cells infiltrate lymph nodes, spleen, thymus or bone marrow. -may also involve other organs- extranodal spread

Chronic Myelogenous Leukemia (CML)

Malignant disease of hematopoetic pluripotent stem cells -endogenous oncogene- t(9,22)- Philadelphia Chromosome -bone marrow and peripheral blood overgrown with malignant stem cells

Multiple myeloma

Malignant disease of plasma cells, patient >45

Thalassemia Types

Minor- Heterozygotes, mild non specific symptoms Major- Homozygotes with severe and serious disases

Heme

Poryphirin ring synthesized in mitochondria and iron is inserted

Clotting Factor II

Prothrombin

Leukopenia

Reduction in WBC to below normal levels -increased risk of infection

Anemia

Reduction of Hg in Blood below normal levels. M<13 g/dL F<11.5 g/dl

Hodgkin Lymphoma

Reed -sternberg cells present Lymph nodes are enlarged (Neck and Mediastium)

Sickle Cell Anemia Symptoms

Retarded intellectual development, cardiopulmonary insufficiency, recurrent infxns

Normocytic Cell SIze

Sickle Cell

Intracorpuscular Defects

Sickle cell anemia, Thallasemia

Treatment Chronic Myelogenous Leukemia

Tyrosine Kinase Inhibitor (Imatinib)

Hematocrit

Volume of packed RBC expressed as % of Total Peripheral Blood. 40% for F, 45% for M. Decreased= Significant Hemorrhage.

Types of Autoimmune Hemolytic Anemia

Warm Ab- Most common form- IgG mediated in Lupus Cold Ab- Mediated by IgM- Chronic patients with mono and lymphoma

Diagnosis Multiple Myeloma

X-ray for lytic lesions Serum electrophoresis (monoclonal spike) Urine contains Bence Jones Protein (IgG) Bone marrow biopsy (increase number of neoplastic plasma cells)

Reed-sternberg cells

bi or multilobed nucleus and prominent nucleoli surrounded by a clear halo

Lymphoma Characteristics

Effects and age group, more common in adults, all malignant, B-cell phenotype

Leukemia

Bone Marrow infiltrated with malignant cells -peripheral blood contains increased number of immature WBC -complications include: anemia, recurrent infxn, uncontrolled bleeding

Autoimmune Hemolytic Anemia

Antibody that destroys RBC from mismatched blood transfusion or Hemolytic Disease of newborn

Extracorpuscular Defects

Autoimmune Hemolytic Anemia and Hemolytic Disease of Newborn

Mean Corpuscular Hemoglobin Concentration (MCHC)

Avg. Concentration of Hg in RBC

Mean Corpuscular Hemoglobin (MCH)

Avg. Mass of Hg per RBC

Mean Corpuscular Volume (MCV)

Avg. Volume of Hemogblobin in RBC

Pathogenesis of Anemia

DECREASED RBC PRODUCTION -Bone Marrow Failure (Aplastic Anemia) -Deficiency of Nutrients- decreased B12 & Folic Acid- Megaloblastic Anemia -Disorder in Synthesis- Defective Heme- Fe 2+ Def Anemia, Defective Globin- Thalassemia ABNORMAL RBC PRODUCTION- Sickle Cell Anemia INCREASED RBC DESTRUCTION- Hemolytic Anemia EXCESSIVE BLEEDING- Heptaglobin in Blood, No Hepatoglobin in Hemolysis

Neutropenia

Decrease in Neutrophil granulocytes- most abundant WBC -Bacterial Infxn

Lymphopenia

Decrease in level of lymphocytes T, B, NK -Bacterial, viral, fungal, parasitic infxn

Megaloblastic Anemia

Deficiency of B12 or Folic Acid Macrocytic cell size

Hemophilia A

Deficiency of Factor VII (Antihemophilic factor)

Hemophilia B

Deficiency of factor IX (plasma thromboplastin component)