HIS01 Structure And Function Of The Haematopoietic System Flashcards
Blood contents
Blood: 8% body weight
- Blood plasma (55%)
- Formed elements (45%)
- RBC (most abundant)
- WBC (neutrophils, lymphocytes, monocytes, eosinophils, basophils)
- Platelets
Haematopoiesis
Process in which Formed elements develop
Red bone marrow is the primary site of haematopoiesis
Major production place:
- Embryo:
- ***Yolk sac
- Liver, Spleen, Thymus, Lymph nodes - 3 months before birth:
- Red bone marrow - 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
- ***Erythropoietin —> RBC
- ***Thrombopoietin —> platelets
- ***Colony-stimulating factors + Interleukins —> WBC
***Myeloid and Lymphoid stem cell
Myeloid stem cell:
- CFU-erythrocyte —> **Proerythroblast —> **Reticulocyte —> RBC
- CFU-megakaryocyte —> **Megakaryoblast —> **Megakaryocyte —> Platelets
- 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
Bone marrow
- 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)
2 major cellular components of Bone marrow
- Parenchymal cells
- Haematopoietic stem cells / Progenitor cells (+ Formed elements) - Stromal cells (Provide micro-environment for haematopoiesis)
- Reticular cells (type of fibroblast)
- Endothelial cells - sinusoids
- Adipose cells
- Macrophages
***Endothelial cells - Sinuses and cords
- 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 - 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
Blood supply to bone marrow
Nutrient artery —> Central sinus —> Emissary vein
Bone marrow cellularity
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
Erythrocytes
- 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)
***Erythropoiesis
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)
Reticulocytes
- 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.)
Erythrocytes death
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.
Blood types
Genetically determined by Antigens —> Glycoproteins + Glycolipids —> Blood types
- ABO blood group: A, B, AB, O
- Rh (Rhesus factor: glycoprotein) blood group: Rh +/-
Wrong blood transfusion —> Agglutination and Hemolysis
***Haemolytic disease of newborn (HDN)
- 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
Platelets
- 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
***Thrombopoiesis
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
Leukocytes / WBC
Granulocytes:
- Neutrophil (pale granules)
- Basophil (blue granules)
- Eosinophil (pink granules)
Agranulocytes / Mononuclear cell:
- Monocyte
- Lymphocyte (T + B cells)
- NK cell
Neutrophil
- 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)
Basophil
- <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
Eosinophil
- 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)
***Granulopoiesis
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
Monocyte
- 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
***Monopoiesis
***Monoblasts —> ***Promonocytes —> Immature monocytes —> Mature monocytes (—> Macrophage migrate into tissue)
- ↓ Cell size
- Progressive indentation of nucleus
Lymphocytes
- 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
***Lymphopoiesis
- Primary lymphoid organ: Red bone marrow + Thymus
- 2 precursor cells: **Lymphoblasts, **Prolymphocytes
—> B, T lymphocytes, NK cells, (Dendritic cells)
Summary of cell production
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
