Haematopoiesis Flashcards
Haematopoiesis occurs earliest in the _________ ______, with erythrocyte and macrophage production.
Yolk sac
Where is primitive erythropoiesis accompanied by haemoglobin variants, such as Portland, Gower I, and Gower II?
Aorta-gonads-mesonephros
In the third month of gestation, the _______ produces erythroid cells and greater numbers of myeloid and lymphoid cells.
Liver
The spleen, _________, and lymph nodes are involved to a lesser degree.
Kidney
The bone marrow is the primary site of haematopoiesis by the __________ month of foetal life.
Sixth
Where is the bone marrow located?
Between the trabeculae of spongy bone
Describe the tissue of the bone marrow.
Cellular, highly-vascularised, loose connective tissue
The ____________ ___________ houses the formation and maturation of haematopoietic and stromal cells.
Haematopoietic compartment
List five features of the vascular compartment.
Nutrient artery
Periosteal arteries
Central longitudinal vein
Arterioles
Sinuses
Haematopoietic cells are arranged in _______ within the marrow cavity.
Niches
Erythroblasts compose 25-30% of the population, and are located near _________ ____________ in the bone marrow.
Venous sinuses
Define erythroblastic islands.
Composed of a single macrophage, surrounded by erythroblasts in different stages of maturation
List three functions of macrophages, in the context of haematopoiesis.
Cytoplasm stretches to contact nearby erythroblasts
Regulates erythropoietin by cytokine secretion
Phagocytose nuclei extruded from erythroblasts
_____________ are produced in nests, close to trabeculae and arterioles, but distant from sinuses.
Granulocytes
Where are megakaryocytes produced?
Near vascular sinuses
Lymphocytes are produced in lymphoid aggregates near ____________.
Arterioles
What is the haematopoietic microenvironment?
An appropriate milieu for the proliferation and maturation of haematopoietic precursor cells (HPCs)
What does the haematopoietic microenvironment consist of?
A complex network of stromal cells and extracellular matrix (ECM) components
Name two types of stromal cells.
Adipocytes
Osteoblasts
What is the function of the adipocytes?
Mechanically mediate the volume of BM in which haematopoiesis occurs, by secreting steroids and cytokines which reinforce osseous integrity and stimulate haematopoiesis
List six features of osteoblasts.
Produce cytokines that regulate stem cell activity
Provide 3-dimensional scaffold for haematopoietic cells
Express homing receptors (e.g., SDF-1, CXCR4, and others)
Produce soluble growth and differentiation factors
Produce integral membrane proteins that function as juxtacrine regulators (SCF, FL, etc..)
Produce ECM components (e.g., highly viscous proteoglycans)
Name four features, and their functions, of the extracellular matrix.
Cytokines and growth factors, to regulate haematopoietic cell differentiation and expansion
Collagen, to provide structural support
Glycosaminoglycans, which provide cell-to-cell interactions; localise growth factors
Cytoadhesion molecules, to allow adhesion of cells to extracellular matrix proteins
HPCs of different lineages and different stages can be found in distinct areas of the marrow called __________.
Niches
True or false: all precursor cells can interact with all areas of the extracellular matrix.
False
The structure of the BM allow for adhesive interactions between the stem cell, progenitor cell, and the ECM function to hold HPCs in microenvironment niches, and to allow for close proximity with _________.
Cytokines
List two other functions of niches.
Important molecular determinant for geographic location
Presence of membrane receptors for ECM proteins
Bone forms a _________compartment for the BM.
Rigid
Any change in volume of haematopoietic tissue must be compensated for by a change in space-occupying ______________.
Adipocytes
At greater than four years of age, adipocytes increase (in ___________ marrow).
Yellow
By ___ years of age, haematopoiesis is limited to marrow of skull, ribs, sternum, scapulae, clavicles, vertebrae, pelvis, upper half of sacrum, and proximal ends of long bones.
25
Red vs. yellow marrow is found in a ratio of _____.
1:1
Define ‘hyperplasia’.
An excessive proliferation of normal haematopoietic cells
List three features of hyperplasia.
Adipocytes may be replaced
Occurs in all conditions with impaired or increased haematopoiesis
Degree is related to severity and duration of the pathological state, as well as the root cause, such as anaemia or leukaemia
When would hypoplasia occur?
When haematopoietic tissue becomes ineffective
What cell type increases in amount in hypoplasia?
Adipocytes
Why would hypoplasia occur?
Caused by genetics and environmental stressors, such as toxins
Where does extramedullary haematopoiesis occur, and why?
Occurs in areas such as the liver and spleen, when hyperplasia of the marrow is unable to cater to haematopoietic needs
Describe the egression of blood cells.
Blood cells migrate from the BM into the circulation by migrating between reticular cells, through endothelial cells, and via cell traffic across the sinuses. Reticular cells contract, creating a less continuous layer over the abluminal sinus walls, and thus producing compartments where mature cells congregate
List three soluble factors required for cells to reach circulation.
Granulocyte-colony stimulating factor (G-CSF)
Granulocyte-monocyte-colony stimulating factor (GM-CSF)
Chemokines
State three features of the thymus.
Lymphopoietic organ
Located in the upper anterior mediastinum
Bilobed
The _________ ________ of the thymus is densely packed with thymocytes, cortical epithelial cells, and some macrophages.
Outer cortex
The __________ __________ of the thymus contains mature thymocytes, epithelial cells, dendritic cells, and macrophages.
Inner medulla
What is the main function of the thymus?
To act as the site of maturation of T-cells
True or false: the spleen is essential to life.
False
The __________ contains the largest collection of lymphocytes and mononuclear phagocytes in the body.
Spleen
Name the three zones of the spleen.
White pulp
Red pulp
Marginal zones
List three features and functions of the white pulp.
Contains lymphocytes
Located around a central artery
Important in immune response
Name two components of the red pulp.
Sinuses and cords
List two features of the marginal zone.
Surrounds white pulp, and is reticular
Contains specialised B-cells, macrophages, and blood vessels
The __________ _______ branches into many vesicles in trabeculae.
Splenic artery
True or false: the spleen’s blood supply may terminate in any of the three main zones.
True
Describe the slow transit pathway of the spleen.
Plasma moves into the sinuses via macrophage-lined cords, involves elevated haematocrit
What other pathway can the spleen operate under?
Rapid transit pathway
Macrophages cull ___________ or damaged red cells.
Senescent
The spleen pits particles, such as antibody, from erythrocytes, without destroying the cells, resulting in _______________.
Spherocytes
For immune defence, the white pulp and marginal zones are rich in lymphocytes and ______________.
Phagocytes
What population is the spleen’s immune function especially important for?
Paediatric
_______ ________ _________ act as reservoirs for platelets.
Red pulp cords
Splenomegaly may result in ____________________.
Thrombocytopaenia
List three findings of hypersplenism.
Enlarged spleen
Exaggeration of normal functions, resulting in anaemia, leucopaenia, and thrombocytopaenia
A hyperplastic BM may exist, corresponding to peripheral blood cytopaenia
__________ hypersplenism has no identifiable cause.
Primary
_____________ hypersplenism occurs in conditions such as hereditary spherocytosis, liver disease, myelofibrosis, immune thrombocytopaenia, etc..
Secondary
Briefly state four other causes of hypersplenism.
Infiltration of the spleen with additional cells or metabolic by-products
Gaucher’s disease, where macrophages accumulate large quantities of undigestible material
Neoplasms in which malignant cells occupy much of the splenic volume
Congestive splenomegaly can occur following liver cirrhosis with portal hypertension, after congestive heart failure, and when blood that does not flow easily through the liver is rerouted through the spleen
_______________ appears to be most beneficial in patients with hereditary or acquired conditions.
Splenectomy
What organ assumes culling functions, in the absence of the spleen?
Liver
__________ cells of the liver can perform functions similar to phagocytes lining splenic cords, but are not as effective as the spleen.
Kupffer
What is functional splenectomy also known as?
Autosplenectomy
List three events to which enhanced sickling of RBCs, due to acidic, hypoxic, and hypoglycaemic environment of the spleen, leads.
Blockage of the blood vessels
Infarcts of the surrounding tissue
Tissue damage becomes progressive and leads to functional splenectomy (autosplenectomy)
State five features of lymph nodes, vessels, and fluids.
Lymph nodes and lymphatic vessels drain into left and right lymphatic ducts
Lymph empties into blood
Vessels originate in connective tissue
Lymph is formed from blood fluid that escapes into tissue
Nodes are bean-shaped
The _________ of a lymph nodes contains B-cell follicles, surrounded by T-lymphocytes and macrophages.
Cortex
Follicles of lymph nodes contain areas of B-cells called _____________ _____________.
Germinal centres
In a lymph node, the _________ surrounds efferent lymphatics.
Medulla
Lymph nodes contain cords of __________ ________, that lie between sinusoids.
Plasma cells
What is the major function of lymph nodes?
To act as filters, removing foreign particles from lymph by phagocytic cells
Antigens in lymph come into contact with, and stimulate, ________________ lymphocytes to proliferate and differentiate into effector cells.
Immunocompetent
Stimulated B-cells move to _________ as plasma cells.
Medulla
What is lymphadenopathy?
The enlargement of the lymph nodes by expansion of the tissue within the node
State four causes of lymphadenopathy.
Inflammation of the lymph node
Prolonged immune response to infectious agents
Malignant transformation of lymphocytes or macrophages
Metastatic tumours that originate in extranodal sites
What does MALT stand for?
Mucosa-associated lymphoid tissue
What is the MALT?
Collection of loosely-organised aggregates of lymphocytes
True or false: the MALT is not as well demarcated as lymph node tissue.
True
What is the main function of the MALT?
To trap antigens
