CH 9- Hematopoietic System Lecture Flashcards

Introduction to the Hematopoietic System and Blood Physiology

• Definition of the Hematopoietic System: This system is responsible for the continuous production of blood cells, a process known as hematopoiesis.

• General Function: It ensures the body maintains an adequate number of red blood cells, white blood cells, and platelets. This maintenance is critical for oxygen transport, immune defense, and hemostasis (blood clotting) throughout a person's life.

• The Three Main Cellular Components:

  • Erythrocytes (Red Blood Cells): Primary agents of oxygen transport.

  • Leukocytes (White Blood Cells): Components of the immune system that fight infection.

  • Thrombocytes (Platelets): Facilitate blood clotting following injury or trauma.

Blood Composition and Components

• Physical Composition: Blood consists of cells suspended in plasma, which is the liquid portion of the blood.

• Functions of Blood: Transports gases, nutrients, waste, hormones, heat, and immune cells throughout the entire body.

• Proportional Composition:

  • Plasma: Makes up approximately $55\%$ of blood volume.

  • Formed Elements: Make up approximately $45\%$ of blood volume (Erythrocytes, Leukocytes, and Thrombocytes).

• Erythrocyte Characteristics and Production:

  • Formation Sites: Formed in red bone marrow found in the vertebrae, proximal femurs, and flat bones (sternum, ribs, skull, and pelvis).

  • Structure: Biconcave discs (indented in the middle). This shape maximizes surface area for gas exchange and allows flexibility to navigate tiny capillaries and vessel branches.

  • Hemoglobin: An iron-based protein packed within red blood cells that carries oxygen from the respiratory tract to bodily tissues.

  • Function: Transporting oxygen to tissues and carrying carbon dioxide back to the lungs.

  • Lifespan: Approximately $120$ days. After this, they are removed by the spleen and liver to be broken down, and the hemoglobin is recycled.

• Leukocyte Characteristics and Classification:

  • Formation Sites: Red bone marrow and lymphoid tissue.

  • Function: Provide immunity and defense against pathogens, cellular debris, and abnormal cells.

  • Granulocytes:

    • Neutrophils: The most abundant white blood cell and first responders to infection; they perform phagocytosis (engulfing bacteria).

    • Eosinophils: Involved in parasitic defense and allergic responses.

    • Basophils: Release histamine (involved in allergies) and heparin (an anticoagulant); they participate in inflammation.

  • Agranulocytes:

    • Lymphocytes: Classified into B cells (antibody production), T cells (cell-mediated immunity), and Natural Killer (NK) cells (destroying abnormal cells).

    • Monocytes: Differentiate into macrophages that perform phagocytosis and antigen presentation.

• Platelets (Thrombocytes):

  • Formation Site: Red bone marrow.

  • Function: Adhere to damaged vessels and aggregate to form temporary plugs and clots while releasing chemicals to activate clotting factors.

• Plasma Detailed Composition:

  • Primarily water with dissolved substances.

  • Proteins: Albumin (maintains osmotic pressure), Globulins (includes antibodies), and Fibrinogen (essential for clot formation).

  • Electrolytes: Sodium, potassium, calcium, chloride, and bicarbonate.

  • Nutrients: Glucose, amino acids, and lipids.

  • Waste Products: Urea (formed by muscle metabolism) and creatinine (found in the kidneys).

Hemostasis, Coagulation, and Blood Typing

• Hemostasis and Coagulation:

  • Hemostasis: The prevention of blood loss while maintaining circulation.

  • Coagulation Cascade: A complex series of enzymatic reactions involving clotting factors produced in the liver. This process requires calcium and Vitamin K.

  • Mechanism: Converts fibrinogen into fibrin. Once healing occurs, the clot is dissolved via fibrinolysis.

• Blood Group Systems:

  • ABO System: Determined by antigens on red blood cell membranes. Plasma contains antibodies against absent antigens.

  • Agglutination: An immune reaction where cells clump together after being bound by antibodies; occurs during incompatible transfusions.

  • Rh Factor: Determines if a patient is Rh-positive (antigen present) or Rh-negative (antigen absent). This is critical in pregnancy.

• Antigens: Molecular structures recognized as either "self" or "non-self" that can trigger immune responses.

• Hematopoiesis Regulation: Controlled by a feedback mechanism involving the brain and endocrine system to adjust production based on blood levels.

• Acid-Base Balance: Blood acts as a buffer to maintain proper pH levels.

Anemia: General Overview and Systems

• Definition: Characterized by a reduction in the oxygen-carrying capacity of the blood, with hemoglobin levels below normal ranges based on age and sex.

• Nature of Anemia: It is not a disease itself but a sign of an underlying physiologic or pathologic process (e.g., cancer, diet, blood loss).

• General Symptoms:

  • Fatigue and weakness (most common).

  • Pallor (pale skin, mucous membranes, nail beds, and conjunctiva).

  • Dyspnea (shortness of breath during exertion).

  • Tachycardia and palpitations (compensatory mechanism where the heart pumps faster to deliver limited oxygen).

  • Dizziness, lightheadedness, syncope, and exercise intolerance.

Iron Deficiency Anemia

• Epidemiology: The most common type of anemia worldwide.

• Etiology:

  • Inadequate iron intake (poor diet, malnutrition, vegetarianism without supplementation).

  • Inadequate iron absorption (celiac disease, Crohn's/IBD, gastric surgery/bypass).

  • Chronic blood loss (GI bleeding, heavy menstruation, frequent blood donations).

  • Increased demand (pregnancy, childhood growth, endurance training).

• Pathophysiology: Results in microcytic hypochromic red blood cells (small and pale) due to impaired hemoglobin synthesis.

• Specific Clinical Manifestations:

  • Koilonychia: Spoon-shaped nails.

  • Glossitis: Smooth, inflamed, sore red tongue.

  • Angular Cheilitis: Cracking and soreness at the corners of the mouth.

  • Pica: Abnormal cravings for non-nutritive substances like ice, clay, dirt, or starch.

• Clinical Significance: Often the first sign of an occult (hidden) disease or bleeding.

• Lab Findings: Decreased hemoglobin, hematocrit, red blood cell count, and serum iron. Decreased ferritin (iron stored in the liver/spleen) is the most sensitive indicator.

• Treatment: Oral iron supplementation (first line), dietary changes, or IV iron for severe cases.

Hemolytic Anemia and Genetic Variants

• Definition: A group of anemias characterized by the premature destruction of red blood cells (hemolysis) where the destruction rate exceeds the bone marrow's production capability.

• Morphology: Usually normocytic (normal size and color).

• Classifications:

  • Intrinsic (Hereditary): Defects within the red blood cell itself (e.g., Hereditary Spherocytosis, Sickle Cell Anemia).

  • Extrinsic (Acquired): Normal cells destroyed by external factors (e.g., Autoimmune Hemolytic Anemia, Erythroblastosis Fetalis).

• Specific Symptoms: Jaundice (yellowing of skin/mucosa), dark urine, enlarged spleen, and gallstones (due to elevated bilirubin).

• Hereditary Spherocytosis:

  • Mechanism: Defects in membrane proteins produce rigid, spherical cells (spherocytes) rather than biconcave discs.

  • Impact: Spleen identifies them as abnormal and destroys them. Most common in Northern European descendants.

  • Aplastic Crisis: A sudden temporary shutdown of red blood cell production.

  • Treatment: Folic acid and potential splenectomy (often delayed until age $3$ to allow immune system development).

• Sickle Cell Anemia:

  • Mechanism: Inherited autosomal recessive disorder involving abnormal hemoglobin.

  • Morphology: Rigid, crescent-shaped (sickle) cells.

  • Impact: Shortened lifespan ($10$ to $20$ days). Cells get trapped, causing vaso-occlusive crisis (severe bone/muscle pain). More common in African descent

  • Specific Manifestations: Dactylitis (sausage-shaped fingers/toes in children), asplenia (non-functional spleen), acute chest syndrome, and stroke risk.

  • Management: Hydroxyurea (to increase fetal hemoglobin), pain management, and transcranial Doppler ultrasound for stroke screening.

• Thalassemia:

  • Population: Common in Mediterranean ancestry.

  • Pathophysiology: Ineffective erythropoiesis and abnormal hemoglobin synthesis. Cells are microcytic and hypochromic.

  • Imaging Findings: "Crew cut" or "hair on end" appearance of the skull on X-ray; "chipmunk face" due to maxillary overgrowth.

  • Complications: Iron overload (from frequent transfusions).

Immune-Mediated and Nutritional Anemias

• Autoimmune Hemolytic Anemia:

  • Acquired/Extrinsic; immune system produces antibodies against its own red blood cells.

  • Symptoms: Acrocyanosis (blue tint to fingers/ears) and Raynaud-like symptoms.

  • Diagnosis: Positive Direct Antiglobulin Test (Coombs test).

• Erythroblastosis Fetalis (Hemolytic Disease of the Newborn):

  • Mechanism: Maternal antibodies cross the placenta and destroy fetal red blood cells due to blood group incompatibility.

  • Rh Incompatibility: Occurs with an Rh-negative mother and Rh-positive fetus. Affects subsequent pregnancies after sensitization.

  • ABO Incompatibility: Affects first pregnancy but is usually milder.

  • Severe Outcome: Hydrops fetalis (generalized edema, ascites, heart failure, and possible fetal death).

  • Prevention: RhoGAM (Rh immunoglobulin) given at $28$ weeks gestation and within $72$ hours postpartum.

• Megaloblastic Anemia:

  • Caused by impaired DNA synthesis due to Vitamin $B_{12}$ or Folate ($B_9$) deficiency.

  • Morphology: Abnormally large immature precursors (megaloblasts).

  • Pernicious Anemia: An autoimmune form of $B_{12}$ deficiency caused by lack of intrinsic factor (secreted by gastric parietal cells) needed for absorption in the terminal ileum.

  • Neurologic Effects: $B_{12}$ deficiency can cause irreversible peripheral neuropathy and gait disturbances.

Bone Marrow Disorders and Polycythemia

• Aplastic Anemia:

  • Bone marrow failure leading to pancytopenia (low red cells, white cells, and platelets).

  • Not a destruction of cells, but a failure of production.

  • Biopsy Finding: Replacement of bone marrow with fat.

• Myelophthisic Anemia:

  • Bone marrow "wasting" or infiltration by abnormal tissue, typically metastatic cancer.

  • Leads to extramedullary hematopoiesis (the liver and spleen try to produce blood), causing hepatosplenomegaly.

• Polycythemia Vera (Primary Polycythemia):

  • A chronic myeloproliferative neoplasm involving overproduction of red blood cells independent of normal regulation.

  • Impact: Increased blood viscosity (thickness), leading to high risk of thrombosis (DVT, stroke, MI).

  • Symptoms: Headaches, dizziness, facial plethora (ruddy complexion), and pruritus (itching) after warm bathing.

  • Treatment: Phlebotomy (bloodletting) to maintain hematocrit less than $45\%$.

• Secondary Polycythemia: Increased red cell mass as a response to hypoxia (e.g., in COPD) or inappropriate erythropoietin secretion.

Leukemias and Lymphomas

• Leukemia: Malignant proliferation of abnormal white blood cell precursors in bone marrow.

• Major Classifications:

  • AML (Acute Myelogenous): Aggressive; common in adults over $60$.

  • ALL (Acute Lymphoblastic): Most common childhood leukemia; aggressive but often curable in children.

  • CML (Chronic Myelogenous): Characterized by the Philadelphia chromosome; can progress to a terminal "blast crisis."

  • CLL (Chronic Lymphocytic): Most common leukemia in Western adults (median age $70$); slow-growing (indolent).

• Leukostasis: A life-threatening emergency in acute leukemia where extremely high white cell counts obstruct small vessels.

• Lymphoma: Malignant solid tumors of lymphoid tissue (B cells, T cells, or NK cells).

• Hodgkin Lymphoma:

  • Marked by Reed-Sternberg cells.

  • Often follows an orderly spread and is highly treatable.

• Non-Hodgkin Lymphoma:

  • More heterogeneous and spreads in a non-contiguous manner.

• Clinical Signs of Lymphoma: Painless lymphadenopathy (firm/rubbery nodes), and "B Symptoms" (unexplained fever, night sweats, weight loss).

• Infectious Mononucleosis (Mono):

  • Acute viral infection caused by the Epstein-Barr Virus (EBV).

  • Known as the "kissing disease" due to transmission via saliva.

  • Classic Triad: Fever, pharyngitis, and lymphadenopathy.

  • Precaution: Avoid contact sports for $3$ to $4$ weeks to prevent splenic rupture due to splenomegaly.

Bleeding and Platelet Disorders

• Hemophilia: Inherited X-linked recessive bleeding disorders affecting primarily males.

  • Type A: Deficiency of Factor $VIII$ (most common, $85\%$ of cases).

  • Type B (Christmas Disease): Deficiency of Factor $IX$.

  • Type C: Deficiency of Factor $XI$ (rare, autosomal recessive, affects both sexes).

  • Clinical sign: Hemarthrosis (bleeding into joints).

• Purpura: Purple skin discoloration from bleeding into skin/mucosa.

• Thrombocytopenia: Low platelet count usually leading to skin/mucosal bleeding (petechiae and purpura).

• Immune Thrombocytopenia (ITP): Acquired autoimmune destruction of platelets.

  • Acute: Common in children following a viral infection; self-limiting.

  • Chronic: Common in adults; requires long-term management.