Haematopoiesis Flashcards
What are the components of blood?
Plasma:
- Water
- Proteins:
- Globulins (y, a, B)
- Albumins
- Fibrinogen
- Small organic compounds and electrolytes
- e.g. glucose, Na+, Ca2+
Red blood cells
White blood cells
What are the roles of albumin?
Maintain oncotic pressure
Acts as a carrier protein for insoluble molecules
Which cells are granulocytes?
Basophils
Neutrophils
Eosinophils
Which cells can differentiate into macrophages?
Monocytes
What are the lifespans of:
- Neutrophils
- Lymphocytes
- Monocytes
- Erythrocytes
- Eosinophils
- Basophils
- Platelets
What % of leukocytes do they make up?
-
Neutrophils:
- 1-2 days
- 60% of leukocyte count
-
Lymphocytes:
- 3 days - 20 years
- 20-30% of leukocyte count
-
Erythrocytes:
- 4 months
- 99% of all blood cells
-
Eosinophils:
- 1-2 days
- 1-3% of leukocyte count
-
Basophils:
- Hours - days
- 0-1% of leukocyte count
-
Platelets:
- 10 days
-
Monocytes:
- 3 days
- 4-10% of leukocyte count
What is haematopoiesis?
Which type of cell is responsible for haematopoiesis?
What processes are involved?
The production of all types of mature blood cells
- Red blood cells = erythropoiesis
- White blood cells = myelopoiesis and lymphopoiesis
- Platelets = thrombopoiesis
Haematopoietic stem cells are responsible for all haematopoetic lineages through:
- Proliferation
- Differentiation
- Maturation
What is the process of haematopoiesis dependent on?
Glycoprotein growth factors produced by bone stromal cells
Except:
- Erythropoetin: produced in the kidneys
- Thrombopoietin: produced by liver
What is differentiation?
New stem cells differentiate into specialised type of cell
What is proliferation?
Mitosis of stem cells to produce greater number of cells
What is maturation?
Maturation of specialised cell to become mature version of that cell.
Define:
Totipotent
Pluripotent
Multipotent
Oligopotent
Unipotent
Totipotent= cells that can differentiate into any cell type including embryonic and extraembryonic
- Initial cells (first cell divisions) of the embryo
Pluripotent= cells that can differentiate into any cell type of the embryo
- Produce the embryo
Multipotent= cells that can differentiate into several different, but related cell types.
Oligopotent= cells can differentiate into a very small number of closely related cell types
Unipotent= cells that can produce more cells of an identical cell type
Describe the process of haematopoiesis
Which cells originate from the common myeloid progenitor cell?
What type of potency does the common myeloid progenitor have?
- Megakaryotes → Thrombocytes
- Erythrocytes
- Mast cells
- Myeloblasts →
- Basophils
- Eosinophils
- Neutrophils
- Monocytes → macrophages
Common myeloid progenitor = multipotent
Which cells originate from the common lymphoid progenitor cell?
Which type of potency does the common lymphoid progenitor have?
- Natural killer cells (large, granular lymphocytes)
- Small lymphocytes →
- T-lymphocytes
- B-lymphocytes → plasma cells
Common lymphoid progenitor = oligopotent
Where do monocytes differentiate into macrophages?
In the tissues
Describe the maturation process of erythrocytes
What is involved in this process?
- Proerythroblast
- Basophilic erythroblast
- Erythroblast
- Orthochromatic erythroblast
- Reticulocyte
- Erythrocyte
Involves:
- Decrease in cell size
- Haemoglobin production
- Loss of organelles (including nucleus)
- Acquisition of biconcave disc shape
Which substance controls the maturation of erythrocytes?
What substances does erythropoiesis require?
Erythropoetin (EPO)
Erythropoiesis requires:
DNA synthesis:
- Folic acid (B9)
- Vit B12 (cobalamin)
- Intrinsic factor
Haemoglobin synthesis:
- Globins a2 and B2 (protein chains)
- Haem (requires Fe2+ and B6)
What is the role of the biconcave disc of erythrocytes?
Increases surface area
Increases flexibility
Minimises distance from surface (enables gas exchange)
What is the role of folic acid (B9) and B12 in erythropoiesis?
What can a lack of either of these substances lead to?
Folic acid is required for DNA synthesis and therefore cellular proliferation
B12 required for the recycling of folic acid
Lack of either of these can lead to megaloblastic anaemia
- Folic acid can ameliorate the effects of B12 deficiency
What is megaloblastic anaemia?
Large erythrocytes made in unsatisfactory amounts
Where is folic acid absorbed?
How long do normal stores last?
How can a folic acid deficiency arise?
Absorbed in the duodenum and jejunum
Normal stores last 3-7 months
Deficiencies can arise from:
- Inadequate dietary intake
- Malabsorption
- Increased demand
- Drugs (e.g alcohol)
Where is B12 (cobalamin) absorbed?
How long do normal stores last?
How can deficiencies arise?
What is required for absorption?
Absorbed in the terminal ileum
Normal stores last 3-4 years
Deficiencies usually arise from malabsorption (rarely inadequate intake)
Intrinsic factor is required for absorption as it binds to B12 and carries it to the terminal ileum where it is absorbed.
What is intrinsic factor? Where it is produced?
Where do deficiencies stem from?
What can deficiencies lead to?
Why is intrinsic factor needed?
Glyprotein produced by parietal cells of the stomach
Deficiencies mainly caused by autoimmune destruction of parietal cells
Deficiencies can lead to pernicious anaemia (form of megaloblastic anaemia- large erythrocytes few in number)
Intrinsic factor is needed for B12 absorption which is required for recycling of B9 which is needed for DNA synthesis.
Name some inherited disorders of globin chains
a or B chain thalassaemia
Sickle cell anaemia
What is sickle cell anaemia?
How is it caused?
Point mutation of base pair: HbA to HbS (A-T becomes T-A)
Leads to erythrocyte deoxygenation which leads to sickle cell shape
How is iron absorbed?
How is it lost from the body?
Dietary iron:
- Some lost in faeces
- Some absorbed into epithelial cells and stored in ferritin pools
- Some absorbed into the blood bound to transferrin
- Some sloughed off due to high turnover of epithalial cells- lost in faeces
Excess iron in blood taken up via the basolateral membrane of GI epithelial cells via ferroportin and bound to ferritin for storage
Where is most absorbed iron transported to?
Mostly transported to bone marrow to make haem.
Remainder stored by the liver and spleen to or used by other tissue cells in enzymatic processes
What is iron deficiency anaemia?
What is it caused by?
Iron deficiency leads to decreased levels of haemoglobin
Low levels of haemoglobin decreases the production of RBCs
Causes:
- Blood loss
- Low dietary intake of iron
- Poor iron absorption
What is pernicious anaemia?
What is it caused by?
Form of megaloblastic anaemia: erythrocytes produced are large but few in number due to deficiency in B12 and/or B9) which leads to decrease number of erythrocytes.
Causes:
- Lack of intrinsic factor
- Diet low in B vitamins
- Decreased absorption of B vitamins
What is aplastic anaemia?
What causes it?
Bone marrow is unable to produce enough RBCs :
- Life threatening
Causes:
- Cancer treatments
- Exposure to toxic substances
- Autoimmune disorders
- Viral infections
What is haemolytic anaemia?
What causes it?
Red blood cells are destroyed faster than bone marrow can produce them
Causes:
- Sickle cell disease
- Thalassaemia
What is anaemia of chronic diseases?
Which chronic disease can this occur in?
Chronic diseases reduce RBC production over a long period of time
Causes:
- Chronic kidney disease
- Rheumatoid arthritis
- Diabetes
- Tuberculosis
- HIV
What is macrocytic anaemia?
Which conditions are included in this classification?
Anaemias causing large erythrocytes, few in number and/or with low Hb count per cell.
Includes:
- Vitamin B12 and B9 deficiency
- Aplastic anaemia
- Liver disease
- Excessive alcohol intake
What is microcytic anaemia?
What is normocytic anaemia?
Microcytic: erythrocytes produced are small and usually have low Hb count per cell.
Normocytic: involves erythrocytes of normal size but low in number
Define:
Hypochromic
Normochromic
Hypochromic: low Hb numbers per RBC
Normochromic: normal Hb number per RBC
What is included under normocytic, normochromic anaemia?
- Blood loss
- Haemolytic anaemia
- Some anaemias of chronic diseases
- Bone marrow failure (not enough erythrocytes produced, those produced are normal)
What is included under microcytic hypochromic anaemia?
- Iron deficiency
- Thalassaemia
- Anaemia of some chronic diseases
Name the types of leukocytes in the diagram
a) Neutrophil
b) Eosinophil
c) Basophil
d) Monocyte
e) Lymphocyte
Define the following white cell disorders:
Leukocytosis
Neutrophilia
Eosinophilia
Lymphocytosis
Leukopenia
What can cause each one?
Leukocytosis: high white cell count
-
Neutrophilia: High neutrophil count
- Acute bacterial infections
- Inflammation
- Tissue necrosis
- Drugs
- Neoplasms
-
Eosinophilia: High eosinophil count
- Allergic disorders e.g. asthma, hay fever
- Lymphocytosis: High lymphocyte count
- Viral infections
Leukopenia: low white cell count
- Aplastic anaemia (low blood cell production in general)
- Hypersplenism
- Sepsis
- Infection
- Drugs
Describe the process of thrombopoiesis
- Megakaryoblast
- Promegakaryocyte
- Megakaryocyte
- Thrombocytes (platelets)
Segments of megakaryocytes project into blood sinusoids.
Blood flow splits off cytoplasmic fragments which become platelets
Define the following platelet disorders:
Thrombocytosis (primary and secondary)
Thrombocytopenia (types)
Thrombocytosis: high platelet count
- Primary: Myeloproliferative disorders
- Secondary: Infection, neoplasms
Thrombocytopenia: low platelet count
-
Decreased proliferation:
- Genetic disorders
- B12 (cobalamin)/ folate deficiency
-
Increased destruction:
- Hypersplenism
- Immune destruction
- Drugs
- Infection
How are erythropoietin and thrombopoietin produced?
What are their roles?
Erythropoietin:
- Produced by fibroblasts in the kidneys in response to cellular hypoxia
- Stimulates erythropoiesis in the bone marrow by binding to receptor on proerythroblasts/basophilic erythroblasts and promotes cell survival (preventing apoptosis)
Thrombopoietin:
- Produced in liver
- Primarily stimulates differentiation of megakaryocytes and thrombocytes.
- Negative feedback loop in which platelets decrease thrombopoietin levels
