01: Hematopoiesis & Leukocyte Disorders

Question 1

ID the components of blood.

Answer 1

• Plasma: albumin, Ig, other proteins
• Cellular component
  
  • ​Buffy coat: WBCs + platelets
  • RBCs

Question 2

Trace out hematopoiesis.

Answer 2

Question 3

Neutrophils

Answer 3

• Most numerous leukocyte
• Polymorphonuclear (PMN), segmented, polys
• Primary defense against infection (“pawns”)
• Phagocytes
• Kill with toxic O2 species
• Neutropenia: ANC < 1,500
  • ​
    ​Severe: ANC < 500
  • Very severe: ANC < 100

Due to infection, medication, blood cancer, autoimmune or inherited

• ​Neutrophilia: ANC > 8,000
  
  • Due to (most to least common) acute infx, corticosteroids, autoimmune dz, leukemoid rxn, blood cancer

Question 4

Bands

Answer 4

• Immature neutrophil
• Present in serious infections: bandemia

Question 5

Lymphocytes

Answer 5

• Second most numerous leukocyte
• Pleiform immune functions:
  
  • Ab production (B cells)
  • Destroy virus-infected & cancer cells (T cells, NK cells)
  • Coordinate immune response
• Lymphopenia: ALC < 1,200
  
  • Due to HIV/AIDS, mediations, viral infx (EBV/CMV), Hodgkins lymphoma

Question 6

Monocytes

Answer 6

• “Garbagemen:” phagocytes
• Antigen-presenting cells
• Differentiate into macrophages in target tissues

Question 7

Eosinophils

Answer 7

• Minor component of blood
• Granules filled with vasoactive compounds
• Fight parasites (?)
• Mediators of allergies
• Eosinophilia (>0.45x10⁹/L)
  
  • Neoplasia
  • Allergy
  • Addisons
  • Collagen-vascular disease
  • Parasites

Question 8

Basophils

Answer 8

• Rarest leukocyte
• Granules contain heparin and histamine (cause allergic response)
• Normal function unclear
• Elevated in hematologic neoplasia

Question 9

Platelets

Answer 9

• Anucleate
• Procoagulant granules
• Key component of hemostasis
• Production driven from megakaryocytes by thrombopoietin
• Lifespan 7-10 days
• Bind to damaged endothelium via von Willebrand Factor (vWF)

Question 10

Platelet production regulation

Answer 10

• Thrombopoietin (drives production) is bound by platelets and megakaryocytes
• Negative feedback: Lots of platelets, lots of thrombopoietin soaked up –> less new platelets produced

Question 11

Erythrocytes

Answer 11

• Anucleate sacks of hemoglobin
• Lifespan = 120 days
• **Reticulocytes **(immature form) = 0.5-1.5% of RBC population (increase in anemia)
• **Erythropoietin **drives production

Question 12

Mean Corpuscular Volume (MCV)

Answer 12

• Measure of the average volume of a red blood corpuscle (RBC)
• Normal = 80-100 fL
• Low = microcytosis, 2/2 low iron
• High = macrocytosis, 2/2 low B12

Question 13

Erythrocyte membrane

Answer 13

• Ion channels in membrane help regulate function
• Proteins (spectrin, ankyrin, band 3, protein 4.2) allow for bending of cytoskeleton –> biconcave disk shape

Question 14

Hereditary spherocytosis/elliptocytosis (poikilocytosis)

Answer 14

• Deficiency of spectrin/ankyrin/band 3/protein 4.2
• Reuslts in formation of spherocytes (no biconcave shape)
• Cells trapped in spleen, undergo hemolysis (–> hemolytic anemia)

Question 15

List the stages of WBC production.

Answer 15

1. Myeloblast
2. Promyelocyte
3. Myelocyte (has “dawn of neutrophil”)
4. Metamyelocyte
5. Band
6. Neutrophil

Question 16

List the stages of RBC prodution.

Answer 16

1. Pronormoblast
2. Basophilic pronormoblast
3. Polychromatophilic pronormoblast
4. Orthochromic pronormoblast
5. Reticulocyte

Question 17

Erythropoietin

Answer 17

• Produced by kidney in response to its own O₂ supply.
• Stimulates erythropoiesis, ↑O₂ delivery.
• Hypoxia induces hypoxia inducible factors (HIF) –> stimulate erythropoietin production.
• Von-Hippel-Lindau (VHL) protein breaks down HIFs.
  
  • Hydroxylated by **PHD2 **(allows binding of VHL to HIFs).
• Mutations in VHL, PDH2, HIF –> congenital polycythaemia (proportion of blood volume that is occupied by red blood cells increases).

Question 18

Morphology of hematopoiesis

Answer 18

• Size inversely proportional to maturity
• Chromatin condenses with maturity
• Key cell features:
  
  • Nuclear:cytoplasmic (N:C) ratio
  • Nuclear shape and location in cytoplasm
  • Color, size of granules
  • Color, shape of cytoplasm

Question 19

Complete blood count (CBC)

Answer 19

• WBC: 4-11 x10⁹/L
  
  • Leukopenia: WBC < 3,000
• Hematocrit (HCT): %vol. of RBCs in blood
  
  • Male = 40-52%
  • Female = 36-58%
• Hemoglobin (Hgb):
  
  • Male = 13.5-17.5 g/dL
  • Female = 11.5-15.5 g/dL
• MCV = 80-100 fL
• Platelets (PLT) = 150-400 x10⁹/L