L01 - Structure and function of the haematopoietic system Flashcards

1
Q

2 major divisions of blood.

A

1) Blood plasma

2) Formed elements: RBC, WBC, Platelets

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2
Q

List the sequential sites of haematopoeisis from embryo to adult.

A

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

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3
Q

List the sequential lineage of haemotopoiesis.

A

Haematopoietic stem cells

Myeloid and lymphoid stem cells

Progenitor cells (colony-forming units)

Precursor cells (blasts)

Formed elements of blood

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4
Q

How is the differentiation of progenitor cells regulated?

A

Erythropoietin – (red blood cells)

Thrombopoietin – (platelets)

Colony-stimulating factors and interleukins (white blood cells)

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5
Q

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

A

• 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

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6
Q

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

A

Present chiefly in axial skeleton and some long bones

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

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7
Q

2 major cellular components and subdivisions of bone marrow?

A

1) Parenchymal cells
- haematopoietic stem cells/ progenitor cells

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

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8
Q

Describe the organization of parenchymal cells in BM.

A

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

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9
Q

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

A

Mature blood cells and platelets in BM sinuses

> > drain in the central sinus
emissary vein
general circulation

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10
Q

Epithelium type of bone marrow sinuses?

A

Discontinuous endothelium

Allow blood cells to leak out into circulation

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11
Q

Define bone marrow cellularity and its trend with age?

A

Ratio of haematopoietic cells to stromal cells (adipocytes)

Decreases with age

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12
Q

Difference in cellularity between leukaemia and aplastic anaemia?

A

Leukaemia = Hypercellular: increased haematopoeitic cells

Aplastic anaemia = Hypocellular, increased adipocyte/ stromal cells

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13
Q

Shape, structural features, function of erythrocytes?

A
  • 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
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14
Q

Differentiation lineage and timeline in erythropoiesis?

A
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)
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15
Q

Changes to RBC during differentiation ineage?

A
  • Cell size decreases, organelles disappear
  • Cytoplasm volume increases
  • Nucleus diminishes in size and eventually vanishes
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16
Q

How does RBC generate ATP?

A

devoid of organelles

> > uses anaerobic fermentation to produce ATP

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17
Q

What metric is Used to measure rate of erythropoiesis ?

A

Reticulocyte count

Mature into red blood cells within 1 to 2 days

Account for 0.5-1.5% of all RBCs

18
Q

What determines blood type?

A
  • Glycoproteins and glycolipids on the surface of RBCs determine blood types
  • Genetically determined by antigens (that react against incompatible antigens on foreign RBCs)
19
Q

List the blood groups.

A

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

Rh blood group
» Rh +/ -

20
Q

Pathogenesis of Hemolytic disease of the newborn (HDN)?

A

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

21
Q

Define chromic and cytic in relation to RBCs.

A

Chromic = colour: normochromic, hypochromic, hyperchromic

Cytic = size: normocytic, macrocytic, microcytic

22
Q

Mechanism of erythropoietin?

A

Liver, kidneys sense hypoxemia (inadequate O2 transport)

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

> > erythropoiesis accelerates

> > Increase RBC count to increase O2 transport

23
Q

Mechanism of degrading RBC and recycling Hb?

A

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
24
Q

Which nutrients are essential for erythropoiesis?

A

Folic acid
Vit B12
Amino acids
Iron

25
What regulates thrombopoiesis?
regulated by thrombopoietin (TPO) produced mainly by liver, also by kidney
26
List 3 functions of platelets and 2 other plasma components essential to platelet function.
* 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
27
Differentiation lineage in thrombopoiesis? | Life span of platelet?
Megakaryoblasts >> Promegakaryocyte >> Megakaryocyte >> Platelet 7 - 10 days
28
Compare the nucleus morphology, size and cytoplasm between cells in the thrombopoiesis lineage?
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
29
Explain why liver cirrhosis can cause thrombocytopenia?
TPO is made in liver Liver cirrhosis = decreased TPO = decreased throbopoiesis Liver cirrhosis = portal hypertension = increase sequestration of platelets in spleen
30
2 classes of leukocytes based on morphology?
1) Granulocytes • Neutrophils • Basophils • Eosinophils 2) Agranulocytes • Monocytes • Lymphocytes (B and T cells) • Natural killer cells
31
Structural features, staining and function of neutrophils?
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
32
Structural features, staining and function of basophils?
- 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
33
Structural features, staining and function of eosinophils
- 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)
34
Differentiation lineage of granulopoiesis?
Myeloblast > Promyelocyte > Myelocyte (neutrophilic, eosinophilic, basophilic) > Metamyelocyte (neutrophilic, eosinophilic, basophilic) > Stab cells (neutrophilic, eosinophilic, basophilic) > Mature cells (neutrophils, eosinophils, basophils)
35
Which precursor cell in granulopoiesis is the largest?
Promyelocyte
36
Describe the change in nucleus shape throughout granulopoiesis.
Myeloblast = large, round, euchromatic Promyelocyte = large, eccentric Myelocyte = Eccentric, Heterochromatic Metamyelocyte = Indented/ kidney shape, heterochromatic Stab cell = Horse-shoe, Heterochromatic Mature cells = specific shapes
37
Structural features, staining and function of monocytes?
- Kidney or horse-shoe nucleus, agranulocyte - Fine azurophilic granules/ lysosomes, Blue/ Grey - Migrate into tissue and increase in number under viral, fungal, bacterial infections >> diff into macrophages
38
Differentiation lineage of monocytes?
Monoblast > promonocyte (55-60h) > monocyte (16h-3d in blood) > macrophage
39
Changes in cell morphology in differentiation of monocytes?
reduction in cell size and the progressive indentation of the nucleus From basophilic to grey-blue colour Appearance of azurophilic granules
40
Structural features, staining and function of lymphocytes?
- 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
41
List all subtypes of lymphocytes?
1. CD4, CD8 T lymphocytes 2. B lymphocytes ``` NK cells (Cytotoxic) Dendritic cells (APC) ```
42
Differentiation lineage of lymphopoiesis?
Lymphoid stem cell: 1) >> Dentritic cells 2) >> lymphoblast >> lymphocytes: a) NK cells b) Small lymphocyte b) i) T cells >> CD4 Helper, CD8 Cytotoxic, Suppressor T cells b) ii) B cells >> Plasma cells or Memory B cells