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HIS > HIS01 Structure And Function Of The Haematopoietic System > Flashcards

HIS01 Structure And Function Of The Haematopoietic System Flashcards

1
Q

Blood contents

A

Blood: 8% body weight

  1. Blood plasma (55%)
  2. Formed elements (45%)
    - RBC (most abundant)
    - WBC (neutrophils, lymphocytes, monocytes, eosinophils, basophils)
    - Platelets
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2
Q

Haematopoiesis

A

Process in which Formed elements develop

Red bone marrow is the primary site of haematopoiesis

Major production place:

  1. Embryo:
    - ***Yolk sac
    - Liver, Spleen, Thymus, Lymph nodes
  2. 3 months before birth:
    - Red bone marrow
  3. Adult:
    - Red bone marrow of ***Vertebral column, Sternum, Ribs, Skull, Pelvis, Proximal ends of femurs
Process:
Haematopoietic stem cells (***pluripotent stem cells)
—> Myeloid + Lymphoid stem cells
—> Progenitor cells (CFU)
—> Precursor cells (Blasts)
—> Formed elements

Hormones are involved to regulate differentiation of progenitor cells

  1. ***Erythropoietin —> RBC
  2. ***Thrombopoietin —> platelets
  3. ***Colony-stimulating factors + Interleukins —> WBC
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3
Q

***Myeloid and Lymphoid stem cell

A

Myeloid stem cell:

  1. CFU-erythrocyte —> **Proerythroblast —> **Reticulocyte —> RBC
  2. CFU-megakaryocyte —> **Megakaryoblast —> **Megakaryocyte —> Platelets
  3. CFU-***granulocyte
  • Myeloblast —> **Promyelocytes —> **Myelocytes —> ***Metamyelocyte
    —> Eosinophilic myeloblast (紅) —> Eosinophil
    —> Basophilic myeloblast (藍) —> Basophil
    —> Myeloblast (普通) —> Neutrophil
  • **Monoblast —> **Promonocyte —> Monocyte (—> Macrophage)
    (4. Mast cell)

Lymphoid stem cell:

  • **Lymphoblast —> ***Prolymphocytes
    1. T-lymphoblast —> T-lymphocyte
    2. B-lymphoblast —> B-lymphocyte (—> Plasma cell)
    3. NK-lymphoblast —> NK cell
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4
Q

Bone marrow

A
  • Connective tissue found in medullary space of bones (space in-between spongy bone)
  • Red bone marrow: present chiefly in Axial skeleton + some Long bones
  • Rate of blood cell formation ↓ as age ↑
    —> red marrow replaced by yellow marrow (mainly fat cells)
    —> remaining place of red marrow: ***Proximal ends of long bone
  • Yellow marrow can revert to Red marrow (e.g. under severe blood loss)
  • Bone marrow examination: **Bone marrow aspiration (samples usually taken from **Iliac crest)
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5
Q

2 major cellular components of Bone marrow

A
  1. Parenchymal cells
    - Haematopoietic stem cells / Progenitor cells (+ Formed elements)
  2. Stromal cells (Provide micro-environment for haematopoiesis)
    - Reticular cells (type of fibroblast)
    - Endothelial cells - sinusoids
    - Adipose cells
    - Macrophages
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6
Q

***Endothelial cells - Sinuses and cords

A
  1. Sinuses / Sinusoids (**Discontinuous capillary):
    - type of capillary (discontinuous basal lamina, incomplete endothelium: allow blood cells to enter general circulation)
    - full of **    mature RBCs (appear pink) / empty space
  2. Cords (running in-between sinuses):
    - **immature blood cells + megakaryocytes
    - clusters of mature **    granulocytes may accumulate at margins of cords
    —> move into sinuses —> general circulation in response to infection / inflammation

Mature blood cells and platelets in sinuses eventually drain in the ***Central sinus
—> general circulation

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7
Q

Blood supply to bone marrow

A

Nutrient artery —> Central sinus —> Emissary vein

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8
Q

Bone marrow cellularity

A

Ratio of Haematopoietic cell : Stromal cells (adipocytes)
—> ↓ with age (∵ ↓ red marrow)
—> give an idea of how bone marrow is functioning (only a finding, not a diagnosis)

Example:
Normal adult: 40-60% cellularity (~1:1 ratio)

Hypercellularity: possible Leukaemia (abnormal growth of cells)
Hypocellularity: possible Aplastic anaemia

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9
Q

Erythrocytes

A
  • Most abundant formed element
  • Transport O2, CO2
  • Biconcave shaped
  • Non-nucleated + devoid of other organelles —> NO metabolic activities
  • Cytoplasm contains haemoglobin —> make blood red, O2 bind to Haem group (CO2 bind to Globin group)
  • Strong, flexible plasma membrane —> not easily ruptured as RBC squeeze into sinusoids
  • Short life cycle (~120 days)
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10
Q

***Erythropoiesis

A

Regulated by Negative feedback

Stimulus:
↓O2 level in blood / Hypoxia (∵ ↓ RBC count / ↓ amount of haemoglobin / ↓ availability of O2)
—> ***Kidney releases Erythropoietin
—> Erythropoietin stimulate red marrow
—> ↑ Erythropoiesis
—> ↑ RBC
—> ↑ O2 carrying ability of blood

Cell development:
- Begins in red marrow with ***Proerythroblast

Haematopoietic stem cells
—> Myeloid stem cells
—> CFU-erythrocytes
—> ***Proerythroblast (***committed to produce RBC, ***earliest identifiable)
—> Erythroblast (Basophilic —> Polychromatic —> Orthochromatic)
—> Normoblast (ejection of nucleus)
—> Reticulocyte (non-nucleated)
—> RBC
  • **As cell matures:
  • Cell size ↓
  • Cytoplasm volume ↑
  • Nucleus size ↓ (eventually vanish)
  • Colour change (basophilic (accumulation of ribosomes) —> red)
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11
Q

Reticulocytes

A
  • Immature RBC
  • ***Non-nucleated
  • **Retain some organelles for haemoglobin synthesis —> **Ribosome / RNA —> Blue colour
  • Mature into RBC in 1-2 days

Reticulocyte count:

  • measure rate of erythropoiesis
  • account of 0.5-1.5% of all RBCs (higher rate: could be due to hypoxia, haemorrhage etc.)
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12
Q

Erythrocytes death

A

Broken up in **Liver + **Spleen
—> Cell fragments (phagocytised)
—> Haemoglobin degraded —> Heme + Globin

Heme
—> ***Biliverdin —> Bilirubin —> Bile —> faeces

Iron
—> Storage / Reuse / Loss by menstruation, injury

Globin
—> Hydrolysed into free a.a.

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13
Q

Blood types

A

Genetically determined by Antigens —> Glycoproteins + Glycolipids —> Blood types

  1. ABO blood group: A, B, AB, O
  2. Rh (Rhesus factor: glycoprotein) blood group: Rh +/-

Wrong blood transfusion —> Agglutination and Hemolysis

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14
Q

***Haemolytic disease of newborn (HDN)

A
  • Rh incompatibility (媽媽有Anti-Rh Ab, 嬰兒有Rh+ RBC)
  • arise during pregnancy
  • normally no Anti-Rh Ab in blood plasma

First pregnancy:
Rh+ blood of foetus enter mother’s circulation
—> mother’s immune system generates Anti-Rh Ab upon first exposure to Rh+ blood
—> if second foetus is Rh+ —> severe consequence

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15
Q

Platelets

A
  • Aka Thrombocytes
  • Regulated by Thrombopoietin (TPO) —> produced mainly by **Liver (also **Kidneys)
  • Small, Non-nucleated

Function:
Haematostasis
1. detect damage to endothelial lining of blood vessels
2. **accumulation to produce blood clot (platelet plug)
3. secrete **adhesive glycoprotein (IIb/IIIa) —> attract other blood cells in ↑ size of plug
4. secrete ***factors —> attract Monocytes, Neutrophils
5. repair damaged blood vessel (when damage site is small enough) —> Clot retraction

Fibrin: cleaved by Thrombin from Fibrinogen, lines outside of platelet plug, attach to other cells —> Cross-linking —> ↑ size of plug

Plasmin: from Plasminogen —> dissolve plug once repair process completed

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16
Q

***Thrombopoiesis

A

Derived from Megakaryoblasts —> Megakaryocytes

  • **Megakaryocytes:
  • Largest cell in bone marrow (larger than Megakaryoblasts)
  • Large, irregular ***nucleus
  • Extensive cytoplasm filled with basophilic granules
  • Platelets formed by ***fragmentation of cytoplasm

Thrombocytopenia: ***Liver failure / Aplastic anaemia

17
Q

Leukocytes / WBC

A

Granulocytes:

  • Neutrophil (pale granules)
  • Basophil (blue granules)
  • Eosinophil (pink granules)

Agranulocytes / Mononuclear cell:

  • Monocyte
  • Lymphocyte (T + B cells)
  • NK cell
18
Q

Neutrophil

A
  • Most abundant (60-70% of all WBC) (最多)
  • Polymorphonuclear granulocytes (PMN)
    —> **Lobulated nucleus connected by strands of **chromatin
    —> older neutrophils more nuclear lobes
  • Neutrophilic
    —> granules do not strongly attract acid / basic stain
    —> clear neutral cytoplasm
  • Response to bacterial infections
    —> Phagocytosis
    —> attracted by chemotactic factors (from dead / damaged cells, tissues, microorganisms)
19
Q

Basophil

A
  • <1% of WBC (最少)
  • Granules: More variable in size + Basophilic (dark purple)
  • Nucleus: Palely basophilic —> usually obscured by density of granules (Blueberry muffin)
  • ↑ in **Allergic reactions
    —> structurally and functionally similar to **    mast cells
    —> granules release **Histamine + **Heparin
20
Q

Eosinophil

A
  • 2-4% of WBC
  • Granules: Uniform-sized + Eosinophilic (pink)
  • Nucleus: ***Bilobed (more visible since stained different colour than granules) (Dumbbell)
  • ↑ in Allergic reactions, Inflammatory responses, **Parasitic infestation
    —> high affinity to Ag-Ab complexes
    —> release chemicals that **    neutralise Histamine —> modulate allergic reactions
    —> combat parasitic worms (    Helminth)
21
Q

***Granulopoiesis

A 
Myeloblast
—> ***Promyelocyte (larger than Myeloblast, start acquiring Azurophilic granules / Primary granules)
—> ***Myelocytes (Secondary granules)
1. Neutrophilic myelocyte
2. Eosinophilic myelocyte
3. Basophilic myelocyte
—> Metamyelocytes
—> Stab cells / Band cells
—> Mature cells (Neutrophil, Eosinophil, Basophil)

Nucleus shape changes:
Oval shape —> More indented (horseshoe / kidney shaped) —> Lobulated

22
Q

Monocyte

A
  • 3-8%
  • NO granules
  • Nucleus: Kidney / ***Horseshoe shaped
  • Cytoplasm: Blue/gray due to presence of **Lysosomes (fine **Azurophilic granules: blue-loving)
  • Travel in blood (non-functional yet) but eventually migrate into tissue —> precursors of Macrophage
  • ↑ in response to Viral, Fungal, Bacterial infections
23
Q

***Monopoiesis

A 
***Monoblasts
—> ***Promonocytes
—> Immature monocytes
—> Mature monocytes
(—> Macrophage migrate into tissue)
  1. ↓ Cell size
  2. Progressive indentation of nucleus
24
Q

Lymphocytes

A
  • 20-30% of WBC (第二多)
  • Small and Large (90% small) —> larger lymphocyte more visible cytoplasm
  • Nucleus: Round
  • Cytoplasm: Blue
  • ↑ number of Large lymphocyte in Acute **Viral infection + **Immunodeficiency diseases
    —> B + T lymphocytes: mediate immune response
    —> NK cells: kill **infected target cells (e.g. cancer cells)
    —> **    Dendritic cells: APC
25
Q

***Lymphopoiesis

A
  • Primary lymphoid organ: Red bone marrow + Thymus
  • 2 precursor cells: **Lymphoblasts, **Prolymphocytes
    —> B, T lymphocytes, NK cells, (Dendritic cells)
26
Q

Summary of cell production

A

RBC:

  • Erythropoietin: Kidney
  • Production: Red bone marrow
  • Destruction: Liver + Spleen
  • Reticulocyte: Non-nucleated

Platelets:

  • Thrombopoietin: Liver (+ Kidney)
  • Megakaryocyte: Nucleated

Lymphopoiesis:
- Primary lymphoid organ: Red bone marrow + Thymus

HIS (30 decks)

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