Leukocytes : Pathophysiology

• Leukopenia


  - low WBC count: less than 4 x 10^9 (4000/mm^3)

  ☆ Granulocytopenia

  ☆ Agranulocytosis
• Granulocytopenia


  - low granulocyte count

  - aka neutropenia

  - predisposes to severe infections

  - can lead to septicemia and death
• Low Granulocyte Count


  - removal rate > production

  - shortened lifespan

  - temporary inflammation

  - splenomegaly
• Granulocytopenia: aka neutropenia


  since 40-75% of granulocytes are neutrophils
• Granulocytopenia: Septicemia


  - significant numbers of active pathogens in the blood

  - can lead to septic shock

  - fatally low BP after. infection
• Agranulocytosis


  extreme shortage or the absence of granulocytes
• Leukopenia: Etiology (4)


  1. Drugs: e.g., cytotoxic drugs, phenothiazines, some sulfonamides, antibiotics

  2. BW Irradiation - e.g., radiotherapy

  3. RBW disorders - e.g., leukemia, some anemias

  4. Severe infections
• Leukocytosis


  high WBC count

  - normal protective reaction in a variety of pathological conditions, especially infections

  - returns to normal when the infection subsides
• Pathological Leukocytosis


  - increased WBC count: 11x10^9/L (11,000/mm^3)

  - unnecessarily sustained

  - can involve more than one type of leukocyte.
• Leukemia


  - uncontrolled increase in the production of leukocytes and/or their precursors

  ☆ Pancytopenia
• In leukemia, leukocyte count abnormally increases.


  In leukemia, leukocyte count isusually raisedbut in some cases itmay be normal or even low.
• Pancytopenia


  caused by leukemic blast cells crowding out other blood

  cells formed in BW
• Leukemia: High risk of infection


  due to immature leukocytes
• Leukemia: Etiology (3)


  1. Ionizing radiation

  2. Chemicals

  3. Genetic factors
• Leukemia: Ionizing radiation


  - from X-rays and radioactive isotopes

  - causes malignant changes in the WBC precursors
• Leukemia: Chemicals


  - mutations in the DNA of the WBC precursors in the BW

  - e.g. benzene, cytotoxic drugs and asbestos
• Leukemia: Genetic Factors


  Identical twins of leukemia sufferers have a much higher risk than normal
• Leukemia: Types (2)


  1. Acute:

  a. myeloblastic (AML)

  b. lymphoblastic (ALL)

  
  

  2. Chronic:

  a. myeloid (CML)

  b. lymphocytic (CLL)
• Acute Leukemias


  - (sudden) affect the poorly differentiated and immature 'blast' cells

  - aggressive diseases, especially in older people

  -usuallyinvolves leukocytosis
• Acute Leukemias affect _ (2)


  1. mucous membranes of the mouth

  2. upper gastrointestinal tract
• Acute Leukemias: Types (2)


  1. Acute Myeloblastic Leukemia (AML)

  2. Acute Lymphoblastic Leukemia (ALL)
• Acute Myeloblastic Leukemia (AML)


  - adults (25-60 y/o)

  - myeloblasts proliferation

  - cured or long-term remission achieved

  
  

  (remission: responsive to treatment)
• Acute Lymphoblastic Leukemia (ALL)


  - children

  - primitive B-lymphocyte

  - 70% achieving cure
• lymphoblasts


  progenitor cells that develop to B cells
• Chronic Leukemias


  - less aggressive than acute forms

  - more differentiated leukocytes

  ✅ leukocytosis
• Leukocytes are more differentiated, i.e. at the _


  Leukocytes are more differentiated, i.e.at the '-cyte
• Chronic Leukemias: Types (2)


  1. Chronic Myeloblastic Leukemia (CML)

  2. Chronic Lymphocytic Leukemia (CLL)
• Chronic Myeloblastic Leukemia (CML)


  - all ages

  - gradual onset

  - may progress to ALL

  - due to Philadelphia chromosome

  - death within 5 years
• a part of chromosome 9 is transferred to chromosome 22
• Chronic Lymphocytic Leukemia (CLL)


  - often in elderly

  - slow disease progression

  - B cells proliferation

  - less aggressive than CML

  - survival until 25 years