Patho

• Erythrocytes (Red Blood Cells-RBCs)

  Biconcave discs, Diameter = approximately 7.5 μm, Thickness=1 μm in center & 2 μm in the periphery, Lack a nucleus and intracellular organelles, Transport O2 and remove CO2, Life span of 120 days before being destroyed in the liver and spleen
• Anemia


  A condition in which hemoglobin level falls below normal with or without decrease in the number of erythrocytes (red blood cells)
• In adult male, hemoglobin < 13.5gm/dl, In adult female, hemoglobin < 11.5gm/dl, In newborn babies, hemoglobin < 14gm/dl
• Causes of Anemia


  • Due to blood loss (Acute Blood Loss Anemia, Chronic Blood Loss Anemia)
  • Due to deficiency of essential factors (Iron deficiency anemia, Vitamin B12 deficiency anemia, Pernicious anemia, Folic acid deficiency anemia)
  • Excessive red cell destruction (Hemolytic anemias)sickle cell anemia
  • Due to bone marrow problem (Aplastic anemia)
• Morphological Classification of Anemias


  • Microcytic & Hypochromic Anemia
  • Macrocytic & Normochromic Anemia
  • Normocytic & Normochromic Anemia
• Blood Indices in different types of Anemias

  Hemoglobin (Hb), RBC count, Packed Cell Volume (PCV), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC)

  
• Iron Deficiency Anemia


  • Commonly seen in infants, children in growing age, pregnancy, old age, Can also be seen due to impaired iron absorption, Anemia is seen when body stores of iron are depleted, Body iron stores are present in bone marrow, liver & spleen, Peripheral blood smear shows microcytic and hypochromic erythrocytes
• Pernicious Anemia


  • Due to autoimmune destruction of gastric mucosa (chronic atrophic gastritis), deficiency of intrinsic factor, Absorption of vitamin B12 does not occur, Megaloblastic anemia occurs, Hypersegmented neutrophils are seen in the peripheral blood film, Macrocytic & normochromic erythrocytes are seen, Shortened life span of RBCs
• Hemolytic Anemias


  • Several causes like sickle cell anemia or hereditary spherocytosis due to genetic defects, Increased erythropoiesis (bone marrow, liver & spleen), RBC precursors are seen in peripheral blood

  
• Aplastic Anemia


  • Failure of bone marrow to produce RBC due to excessive irradiation, cytotoxic drugs in malignancy, Pancytopenia (usually), Idiopathic (65% cause unknown), Anemia, bleeding, infection
• Polycythemia


  Raised erythrocyte number per unit volume of blood for a particular age and sex
• Types of Polycythemia


  • Primary Polycythemia (Polycythemia vera/Erythremia)
  • Secondary Polycythemia
• Primary Polycythemia


  • Always pathological, Neoplastic/Cancerous, Genetic abnormality with stem cells, Hb, RBC, PCV, Platelets, Leucocytes show an increase
• Secondary Polycythemia


  • Physiological (High altitude), Pathological (Erythropoietin secreting tumors of kidneys), Hb, RBC, PCV, erythropoietin show an increase
• Normal reference ranges of Leukocytes (WBCs)


  • Neutrophils (54% - 62%)
  • Eosinophils (1-3%)
  • Basophils (0-1%)
  • Lymphocytes (25-33%)
  • Monocytes (3-7%)
• Leukocyte Abnormalities


  • Leukocytosis (Bacterial infections, Acute tonsilitis, Pneumonia, Urinary tract infection)
  • Leukocytopenia (Viral infections, Influenza, Aplastic anemia, Tuberculosis)
• Reactive proliferations of WBC's

  • Neutrophils (Neutrophilia)
  • Lymphocytes (Lymphocytosis)
  • Eosinophils (Eosinophilia)
  • Basophils (Basophilia)
  • Monocytes (Monocytosis)
• Acute leukemia


  Characterized by an abnormal proliferation of immature white blood cells, called blasts or progenitor cells
• Forms of acute leukemia


  • Acute lymphoblastic leukemia (A cancer at the earliest stages of lymphocyte maturation, Occurs more often in the young)
  • Acute nonlymphoblastic leukemia (Usually a malignancy of the myeloblast, More common in adults)
• Functional Presentation of Leukemia


  • People with leukemia present with signs and symptoms of low red blood cell count (anemia), decreased white blood cells (granulocytopenia) with infection and fever, and low platelet count (thrombocytopenia) with bleeding, People will usually present critically
• Cell-mediated Immunity


  Role of T-lymphocytes
• Types of T-lymphocytes


  • Helper T-cells
  • Cytotoxic T-cells
  • Suppressor T-cells
• Helper T-cells


  • Most numerous of all the T-cells (75%)
  • CD 4 receptors
  • Produce interleukins
  • IL-2 stimulates growth & proliferation of cytotoxic & suppressor T-cells
  • Stimulates growth & proliferation of B-cells alongwith plasma cells (IL-4,5,6)
  • IL-2 exerts positive feedback effect upon helper T-cells for further proliferation
  • Play an important role in inflammation & delayed hypersensitivity
  • Inactivated by HIV virus (AIDS)

  
• Cytotoxic T-cells


  • CD 8 receptors
  • Can directly attack & kill invaders
  • Produce hole-forming proteins called PERFORINS
  • Play role in transplant rejection, destroy cancer cells
• Suppressor T-cells


  • Regulate the activity of helper & cytotoxic T-cells
  • Important role in IMMUNE TOLERANCE / SELF TOLERANCE
  • Immune tolerance protects individual's own body cells from the attack by cytotoxic T-cells
  • Failure of immune tolerance leads to auto-immune diseases
• Autoimmune Diseases


  • Glomerulonephritis
  • Rheumatoid arthritis
  • Multiple sclerosis
  • Myasthenia gravis
  • Systemic lupus erythematosus
• Immunosuppressive therapy


  • Drug regimen that patients use to lower their bodies' immune response
  • Helps stop the immune system from overreacting and damaging transplanted organs and tissues
  • Everyone has to take immunosuppressant drugs when receiving an organ transplant
• Humoral Immunity


  • Mediated by antibody formation in response to a foreign antigen/invader
  • Lymphokines from helper T-cells cause proliferation of B-cells & transformation into plasma cells
  • Plasma cells will then make antibodies (immunoglobulins) to kill the foreign invaders
• Thrombocytopenia


  • Low platelet count (Platelet count of 50,000/cmm or less)
  • Characterized by prolonged bleeding time
  • Bleeding from small venules & capillaries
  • Small punctate hemorrhages in skin & mucous membrane
  • Gingival (gums) & nasal bleeding common
• Types of Hemophilia


  • Hemophilia A (85%)
  • Hemophilia B (15%)
  • Hemophilia C
• Hemophilia A


  • Due to deficiency of clotting factor VIII
  • X-chromosome linked recessive disorder
  • Males are sufferers and females are carriers
  • Sufferer males will transmit disease to all female children but not to male children
  • Bleeding normally does not occur except when there is trauma
  • Bleeding from large blood vessels (Epistaxis, hematuria, hemarthroses)
  • Hemophiliacs are prone to AIDS due to multiple blood transfusions
• Hemophilia B


  • Also called factor IX deficiency or Christmas disease
  • A genetic disorder caused by missing or defective factor IX
  • Caused by an defective gene located on the X chromosome
  • Males have only one X chromosome, so if the factor IX gene is missing, he will have Hemophilia B
  • Causing easy bruising and bleeding due to missing of factor IX
• Thrombosis

  • The disease occur when endothelium is damaged
  • Also occurred by increased platelet count or adhesiveness, increased clotting factors, atherosclerosis, decreased nitric oxide, prolonged bed rest & slow moving blood
• Embolism


  • When a bit of thrombus is detached and on being carried by blood obstructs some blood vessels, the condition is called thromboembolism and the detached pieces are called emboli
  • The usual forms are pulmonary embolism and cerebral embolism
• Natural anticlotting mechanisms

  • Smoothness of normal endothelial lining
  • Antithrombin III
  • Antithromboplastin
  • Heparin
  • Protein C
  • Fast velocity of the blood flow in larger blood vessels
• Acquired Immunodeficiency Syndrome (AIDS)


  • Chronic, potentially life-threatening condition caused by HIV
  • HIV interferes with body's ability to fight infection and disease by damaging immune system and infecting/killing CD4 cells
• Modes of Spread of AIDS

  • INTRAVENOUS DRUG ABUSE
  • HOMOSEXUALITY
  • HETEROSEXUALITY
• AIDS-related cancers


  • KAPOSI SARCOMA
  • B-CELL LYMPHOMAS
  • CNS LYMPHOMAS
  • CANCER OF CERVIX
• Types of Hypersensitivity Reactions


  • Type I Hypersensitivity (Immediate Hypersensitivity)
  • Type Il Hypersensitivity (Antibody Mediated Hypersensitivity)
  • Type Ill Hypersensitivity (Immune-Complex Mediated Hypersensitivity)
  • Type IV Hypersensitivity (Cell-Mediated/ Delayed Hypersensitivity)
• Type I Hypersensitivity (Immediate Hypersensitivity)


  • "Immediate" means within seconds to minutes
  • Allergen exposure leads to IMMEDIATE phase: MAST cell degranulation, vasodilatation, vascular leakage, bronchospasm
  • LATE phase (hours to days): Eosinophils, neutrophils, T-Cells are involved