Hematopoietic System, Coagulation and the Lymphoid System

• Development
  –  Yolk sac in embryo
  –  All bones, liver and spleen in fetus
  –  All bones except face in child
  –  Calvarium, sternum, ribs, vertebrae, pelvis and clavicles in adult (axial skeleton)
• Red and yellow marrow
• Reserve
  –  Extramedullary hematopoiesis
   
  Blood
• Blood smear
• Gross examination
  –  Plasma versus serum
  –  Hematocrit
• Cellular elements
• Salts: most common?
• Proteins: two predominate
• Carbohydrates, lipids, gases
  
  Anemia
• Erythrocytes transport oxygen
  –  Easily deform and reseal
  –  Shape determined by hemoglobin
  –  Life span 120 days (longest of blood cells)
• Hemoglobin
  –  Heme = pyrrole rings and iron
• Bilirubin from pyrrole rings (spleen)
  –  Iron, B12, B6, folic acid, protein
• MCV, MCH, MCHC
   
  Understanding Anemia
   
• The Factory: Status of Marrow
• The Red Cell
  –  Structure
  –  Environment
  –  Clearance
• The Circulation: Is it intact?
• Etiology
• Morphology
  Effects
• Hypoxemia
• Dizziness, fainting, lethargy
• Murmurs and heart failure
• Angina
• Claudication
• Pallor
   
  Aplastic anemia
• Failure of the marrow
  –  Developmental- Name a cause?
  –  Radiation
  –  Toxic substances: lead, toluene
  –  Immune attack
  –  Cancer
  –  Idiopathic
• Normocytic normochromic
• Treatment?
  Megaloblastic anemia
• Pernicious anemia
• Defective intrinsic factor production (aging)
  –  Autoimmune
• Vitamin B12
• Develops slowly so severe when recognized
• Affects spinal cord (demyelinization of posterior and lateral columns
  –  Loss of position and vibratory sensation
• Folic acid- need extra in pregnancy
   
  Microcytic Hypochromic Anemia
    
• Iron deficiency anemia
  –  MOST COMMON ANEMIA HERE
  –  Blood loss
• 2-4 ml/day sufficient to cause this anemia
  –  Abnormal diet
  –  Pregnancy
  –  Note: Sudden loss (trauma) does not cause a microcytic hypochromic anemia! Why?
   
  Disorders of hemoglobin
   
• Sickle cell disease/trait
  –  Infarcts and skin ulcers, aseptic necrosis of bone
  –  Pain
  –  Splenomegaly (removal of cells) then atrophy (infarcts)
  –  Infection
• Thalassemia
  –  Major (homozygous) versus minor,         
  –   Beta (2) versus alpha (4) chains
   
  Other Anemias
   
  
• Importance of shape: hereditary spherocytosis
• Parasites
  –  Hookworm
  –  Malaria
  –  Babesia
• Trauma
  –  Fibrin
  –  Valves and other appliances
   
  Blood Typing & Rh Disease
   
  
• Difference between the ABO and Rh antigens
  –  Chemistry
  –  Cells that display them
• Typing and Crossmatching
  –  THE NUMBER ONE ERROR
• Erythroblastosis fetalis
  –  Hydrops, anemia, kernicterus
  –  Preventable (RhoGam)
   
  Polycythemia
   
  
• Primary: a malignancy
• Secondary: prolonged anoxia
  –  High altitude
  Disorders of White Cells
• Functions
  –  Neutrophil, monocyte, eosinophil
• Leukopenia
  –  Virus: HIV (AIDS): CD4 (helper cell)
• Leukocytosis
  –  Inflammation
  –  Infection
• Infectious mononucleosis
   
  Lymphoma & Leukemia
   
  
• Etiologies
  –  Viruses: EBV, HTLV-1
  –  Oncogenes
• Translocations: Philadelphia chromosome (22 to 9)
• Signs and symptoms
  –  Anemia
  –  Infection
  –  Bleeding
  –  Enlarged spleen and/or lymph nodes
   
  Acute Lymphoblastic Leukemia
   
  
• 5 years and older population
• Most common childhood leukemia
• Rapid course: bleeding, weakness, infection
• Chemotherapy effective- 50% cured
• B cell type does best
   
  Acute Myelogenous Leukemia
   
  
• Mixed varieties, varied features
• Most common leukemia
• In older individuals
• Bone marrow transplantation
   
  Chronic Myelogenous Leukemia
   
  
• Occurs in adults
• 90% with Philadelphia chromosome (Ph1)
• High white count; all stages
• Large spleen
• Insidious onset
• Ends in blast crisis
• Bone marrow transplantation
   
  Chronic Lymphocytic Leukemia
   
  
• Gene bcl-2 immortalizes lymphocytes
• Older population
• Slowly progressive (survival 5-10 years)
• Does not respond well to chemotherapy
   
  Lymphomas
   
  
• Hodgkin's Disease and non-Hodgkin's lymphomas
• Non-Hodgkin's
  –  Follicular versus diffuse
• Low grade
• Intermediate grade
• High grade
  –  Lymph nodes then extra-nodal (staging)
  –  Symptoms: hyper metabolism
• Fatigue, malaise, weight loss, pruritus, sweating
   
  Types of Lymphomas
   
  
• Follicular: usually B-cell
  –  Commonest
  –  Low grade
• Diffuse large cell: B or T
  –  Several types
  –  Intermediate to high grade
• Burkitt’s or Burkitt’s-like
  –  Stem cells, EBV associated
  –  Children and young adults
   
  Hodgkin’s Disease
   
  
• Bimodal: 20-30, 45-55
• Four types
• Reed-Sternberg cell
• Node enlargement
• Favorable prognosis
   
  Multiple Myeloma
   
  
• Tumor of plasma cells
• Increasing in frequency
• Older age group
• Vertebrae and other bones
• Abnormal immunoglobulin
• Diagnosis by electrophoresis and Immunoelectrophoresis
   
  Coagulation
   
  
• Vessels (not arteries)
• Platelets
  –  Megakaryocytes
• Coagulation proteins
• Petechiae and ecchymoses
• Thrombi and clots
   
  The Cascade Principals
   
  
• Surface (on platelets, damaged endothelium)
• Amplification
• Positive and negative feedback
• Localization
• Inhibitors
  –  Soluble activated factors
  –  Flow
• Lysis of thrombi: plasmin and others
   
  Disorders of Coagulation
   
  
• Diseases of vessels: senile purpura
• Disorders of platelets
  –  Autoimmune thrombocytopenia
  –  ITP (idiopathic thrombocytopenic purpura)
• Disorders of coagulation factors
  –  Hemophilia
  –  DIC (disseminated intravascular coagulation)
  –  Liver disease
   
  Testing Coagulation
   
  
• Bleeding time: Everything including    platelets and vessels
• Prothrombin time: Factors that need Vitamin K: coumadin rx
• PTT (partial thromboplastin time): prothrombin, V, VIII, IX, X
  –  Screening for factor deficiency
• Clotting time: fibrin, platelets
• Platelet count: platelets
  Anticoagulant
   
  
• Heparin: parenteral, fast acting
  –  Green tube
• Coumadin
• Citrate (blood donation)
  –  Blue tube
• Aspirin
• EDTA (coagulation studies)
  –  Lavender tube
• Antibody (Go to the Library)