L01 - Structure and function of the haematopoietic system

Question 1

2 major divisions of blood.

Answer 1

1) Blood plasma

2) Formed elements: RBC, WBC, Platelets

Question 2

List the sequential sites of haematopoeisis from embryo to adult.

Answer 2

3rd week-3 months of gestation: yolk sac (mostly RBC)

1 month of gestation-birth: fetal liver

3-6 months of gestation: spleen

4 months of gestation-birth: red bone marrow, lymphatic tissue- Lymph nodes

Adult: Bone marrow of skull, ribs, sternum, vertebral column, pelvis, proximal ends of femurs

Question 3

List the sequential lineage of haemotopoiesis.

Answer 3

Haematopoietic stem cells

Myeloid and lymphoid stem cells

Progenitor cells (colony-forming units)

Precursor cells (blasts)

Formed elements of blood

Question 4

How is the differentiation of progenitor cells regulated?

Answer 4

Erythropoietin – (red blood cells)

Thrombopoietin – (platelets)

Colony-stimulating factors and interleukins (white blood cells)

Question 5

Location of bone marrow in bone? Rate of blood cell formation and type of marrow change with age?

Answer 5

• Connective tissue found in the medullary space of bones (surrounded by spongy bone)

Rate of blood cell formation decreases as an individual ages
• Red marrow replaced by yellow marrow
• Yellow marrow is mainly adipose cells: retain hematopoietic potential during severe blood loss

Question 6

Location of bone marrow in the skeleton? Where to extract bone marrow for examination?

Answer 6

Present chiefly in axial skeleton and some long bones

Samples are usually taken from the iliac crest of the hip bone

Question 7

2 major cellular components and subdivisions of bone marrow?

Answer 7

1) Parenchymal cells
- haematopoietic stem cells/ progenitor cells

2) Stromal cells
- Reticular cells, endothelial cells, adipose cells, macrophages
- Provide microenvironment for haematopoiesis

Question 8

Describe the organization of parenchymal cells in BM.

Answer 8

Hematopoietic stem cells (HSCs): densely packed cords and islands between meshwork of vascular sinusoids

Sinuses: full of mature RBCs

Cords: immature blood cells and megakaryocytes

Clusters of mature granulocytes may accumulate at margins of cords

Question 9

How do mature blood cells in the marrow reach the blood circulation?

Answer 9

Mature blood cells and platelets in BM sinuses

> > drain in the central sinus
emissary vein
general circulation

Question 10

Epithelium type of bone marrow sinuses?

Answer 10

Discontinuous endothelium

Allow blood cells to leak out into circulation

Question 11

Define bone marrow cellularity and its trend with age?

Answer 11

Ratio of haematopoietic cells to stromal cells (adipocytes)

Decreases with age

Question 12

Difference in cellularity between leukaemia and aplastic anaemia?

Answer 12

Leukaemia = Hypercellular: increased haematopoeitic cells

Aplastic anaemia = Hypocellular, increased adipocyte/ stromal cells

Question 13

Shape, structural features, function of erythrocytes?

Answer 13

• Function in transporting O2 and CO2
• Biconcave shaped
• Non-nucleated and devoid of other organelles
• cytoplasm contains haemoglobin
• Cytoskeletal proteins (spectrin, actin) provide resilience, durability

Question 14

Differentiation lineage and timeline in erythropoiesis?

Answer 14

Differentiation phase (~5 days) 
Maturation phase (~ 2 days) 

Myeloid stem cell 
>> Hemocytoblast (Day 1)
>> Proerythroblast 
>> Early/ Late erythroblast (Day 2-3)
>> Normoblast (Day 4)
>> Reticulocyte (Day 5-7)
>> Erythrocyte (Day 7)

Question 15

Changes to RBC during differentiation ineage?

Answer 15

• Cell size decreases, organelles disappear
• Cytoplasm volume increases
• Nucleus diminishes in size and eventually vanishes

Question 16

How does RBC generate ATP?

Answer 16

devoid of organelles

> > uses anaerobic fermentation to produce ATP

Question 17

What metric is Used to measure rate of erythropoiesis ?

Answer 17

Reticulocyte count

Mature into red blood cells within 1 to 2 days

Account for 0.5-1.5% of all RBCs

Question 18

What determines blood type?

Answer 18

• Glycoproteins and glycolipids on the surface of RBCs determine blood types
• Genetically determined by antigens (that react against incompatible antigens on foreign RBCs)

Question 19

List the blood groups.

Answer 19

4 different types: A, B, AB, O:
AB+ = universal recipient
O- = universal donor

Rh blood group
» Rh +/ -

Question 20

Pathogenesis of Hemolytic disease of the newborn (HDN)?

Answer 20

Rh incompatibility, Arise during pregnancy

Normally no anti-Rh antibodies in Rh -ve mother blood plasma

If first fetus is Rh+, then mother’s immune system generates antibodies against Rh+ blood

If second fetus is also RH+, mother’s anti-Rh Ab attack fetal blood

Question 21

Define chromic and cytic in relation to RBCs.

Answer 21

Chromic = colour: normochromic, hypochromic, hyperchromic

Cytic = size: normocytic, macrocytic, microcytic

Question 22

Mechanism of erythropoietin?

Answer 22

Liver, kidneys sense hypoxemia (inadequate O2 transport)

> > secrete erythropoietin (EPO): stimulates red bone marrow

> > erythropoiesis accelerates

> > Increase RBC count to increase O2 transport

Question 23

Mechanism of degrading RBC and recycling Hb?

Answer 23

Erythrocytes circulate for 120 days

Expired erythrocytes break up in liver, spleen:

Hb degradation
- Heme > Biliverdin > bilirubin > bile > feces

• Iron > stored for reuse
• Globin > hydrolyzed to free amino acids

Question 24

Which nutrients are essential for erythropoiesis?

Answer 24

Folic acid
Vit B12
Amino acids
Iron

Question 25

What regulates thrombopoiesis?

Answer 25

regulated by thrombopoietin (TPO)

produced mainly by liver, also by kidney

Question 26

List 3 functions of platelets and 2 other plasma components essential to platelet function.

Answer 26

• Platelet surface for coagulation factor reactions
• Produce a blood clot (a platelet plug) +Secrete adhesive glycoproteins = increase aggregation
• Repair damaged blood vessels, clot retraction

Fibrin, Plasmin

Question 27

Differentiation lineage in thrombopoiesis?

Life span of platelet?

Answer 27

Megakaryoblasts
» Promegakaryocyte
» Megakaryocyte
» Platelet

7 - 10 days

Question 28

Compare the nucleus morphology, size and cytoplasm between cells in the thrombopoiesis lineage?

Answer 28

Increase in size, nucleus size, basophilic staining:

Megakaryoblasts: 15-25 µm, Round, Bi-nucleated with many nucleoli, Basophilic

Promegakaryocyte: 45 µm, Large irregular nucleus, More basophilic

Megakaryocyte: 70-90 µm, Large clumped nucleus, highly basophilic with granules

Question 29

Explain why liver cirrhosis can cause thrombocytopenia?

Answer 29

TPO is made in liver
Liver cirrhosis = decreased TPO = decreased throbopoiesis

Liver cirrhosis = portal hypertension = increase sequestration of platelets in spleen

Question 30

2 classes of leukocytes based on morphology?

Answer 30

1) Granulocytes
• Neutrophils
• Basophils
• Eosinophils

2) Agranulocytes
• Monocytes
• Lymphocytes (B and T cells)
• Natural killer cells

Question 31

Structural features, staining and function of neutrophils?

Answer 31

Most abundant

• Polymorphonuclear granulocytes (3-5 Lobules nucleus connected by strands of chromatin)
• Neutrophilic (Clear neutral cytoplasm)
• Acute inflammatory response to bacterial infections: Phagocytosis, Attracted by chemotactic factors, antimicrobial granules

Question 32

Structural features, staining and function of basophils?

Answer 32

• Least abundant, same size as eosinophil
• Densely packed with basic, blue granules containing histamine, heparin, serotonin
• Hidden, Bi-lobed nucleus
• Function similar to mast cells: Chemotaxis, anticoagulate, vasodilate in Viral infection, inflammation, Allergic reactions

Question 33

Structural features, staining and function of eosinophils

Answer 33

• Larger than neutrophil, same as basophil
• Large, acidophilic/ red granules, same size
• Bilobed nucleus
• Allergic reaction, inflammation, parasitic infection:
  • High affinity to antigen-antibody complexes
  • Release chemicals that neutralise histamine
  • Combat parasitic worms (helminth)

Question 34

Differentiation lineage of granulopoiesis?

Answer 34

Myeloblast
> Promyelocyte
> Myelocyte (neutrophilic, eosinophilic, basophilic)
> Metamyelocyte (neutrophilic, eosinophilic, basophilic)
> Stab cells (neutrophilic, eosinophilic, basophilic)
> Mature cells (neutrophils, eosinophils, basophils)

Question 35

Which precursor cell in granulopoiesis is the largest?

Answer 35

Promyelocyte

Question 36

Describe the change in nucleus shape throughout granulopoiesis.

Answer 36

Myeloblast = large, round, euchromatic

Promyelocyte = large, eccentric

Myelocyte = Eccentric, Heterochromatic

Metamyelocyte = Indented/ kidney shape, heterochromatic

Stab cell = Horse-shoe, Heterochromatic

Mature cells = specific shapes

Question 37

Structural features, staining and function of monocytes?

Answer 37

• Kidney or horse-shoe nucleus, agranulocyte
• Fine azurophilic granules/ lysosomes, Blue/ Grey
• Migrate into tissue and increase in number under viral, fungal, bacterial infections&raquo_space; diff into macrophages

Question 38

Differentiation lineage of monocytes?

Answer 38

Monoblast

> promonocyte (55-60h)

> monocyte (16h-3d in blood)

> macrophage

Question 39

Changes in cell morphology in differentiation of monocytes?

Answer 39

reduction in cell size and the progressive indentation of the nucleus

From basophilic to grey-blue colour

Appearance of azurophilic granules

Question 40

Structural features, staining and function of lymphocytes?

Answer 40

• 90% small lymphocytes, smallest WBC
• Acute viral infection and immunodeficient diseases cause increase number of large lymphocytes
• Blue, basophilic granules
• Round nucleus, narrow rim of blue cytoplasm

Question 41

List all subtypes of lymphocytes?

Answer 41

1. CD4, CD8 T lymphocytes
2. B lymphocytes

NK cells (Cytotoxic)
Dendritic cells (APC)

Question 42

Differentiation lineage of lymphopoiesis?

Answer 42

Lymphoid stem cell:

1)&raquo_space; Dentritic cells
2)&raquo_space; lymphoblast&raquo_space; lymphocytes:
a) NK cells

b) Small lymphocyte
b) i) T cells&raquo_space; CD4 Helper, CD8 Cytotoxic, Suppressor T cells
b) ii) B cells&raquo_space; Plasma cells or Memory B cells