Haemopoiesis, the Spleen and Bone Marrow Flashcards
What is haemopoiesis
Process by which blood cells are formed
Where does haemopoiesis take place
In the bone marrow, mainly in pelvis, sternum, skull, ribs and vertebrae
What cell is in the bone marrow that differentiates into blood cells
Haemopoietic stem cell (multipotential)
What are the five main lineage pathways arising from haemopoietic stem cells
Thrombopoiesis
Granulopoiesis
Monocytopoiesis
Lymphopoiesis
Erythropoiesis
What is thrombopoiesis
Production of platelets - platelets are membrane bound fragments which bud off from megakaryocytes
Megakaryocyte formation is driven by thrombopoietin (TPO)
What are the cells produced by granulopoiesis
Granulocytes - basophils, neutrophils and eosinophils
What is granulopoiesis
Production of granulocytes from myeloblast cells
Myeloblast cells airse from common myeloid progenitor cells
What is the function of neutrophils
Migrate to areas of inflammation by chemotaxis where they phagocytose invading microbe and destroy them by respiratory burst
What is the function of eosinophils
Phagocytose microbes and are associated with immune response to multicellular parasites
What is the function of basophils
Role similar to eosinophils in parasitic infections and allergy
What is monocytopoiesis
Production of monocytes from myeloblast cells
Myeloblast cells airse from common myeloid progenitor
What is lymphopoiesis
Production of B and T lymphocytes from small lymphocytes which arise from common lymphoid progenitors
How do B lymphocytes develop
Start development in foetal liver and bone marrow
During development, immunoglobulin genes rearrange to allow production of antibodies with wide range of specificities
Final maturation of B-cells requires exposure to antigen in lymph nodes
How do T lymphocytes develop
T-lymphocyte progenitors arise from foetal liver and migrate to thymus gland early in gestation
Immature T-cells undergo rearrangement of T-cell receptor genes resulting in ability to produce wide range of T-cell receptors
What is erythropoiesis
Process by which erythrocytes are produced in the bone marrow
What hormone drives erythropoiesis and where is it produced
Erythropoietin
Produced by the kidneys
What factors cause an increased erythropoietin production
Hypoxia caused by:
Decreased RBC count
Decreased Hb
Decreased oxygen availability
What is the function of erythropoietin
Inhibit apoptosis of CFU-E (colony-forming units of erythroid cell line) progenitor cells
Allow these cells to develop, proliferate and differentiate
How do erythrocytes develop
Nucleated erythroblasts extrude their nuclei and most organelle forming reticulocytes
Reticulocytes are released into circulation where they extrude remaining organelle to form erythrocytes
What proteins are found in the erythrocyte cell membrane
Spectrin
Ankyrin
Band 3
Protein 4.2
What is the function of the proteins found in the RBC membrane
Facilitate vertical interactions with cell cytoskeleton and are essential in maintaining the RBCs biconcave shape and deformability
What disease is associated with a mutation in RBC membrane proteins
Hereditary spherocytosis
What is the spleen split into and what cells go into the different parts
Red pulp - sinuses lined by endothelial macrophages and cords. RBCs pass through red pulp
White pulp - structure similar to lyphoid follicles. White cells and plasma passes through here
What is the spleen’s functions
Sequestration and phagocytosis
Blood pooling
Extremedullary haemopoiesis
Immunological functions - antibody synthesis, removal of antibody-coated bacteria
Red pulp removes old RBCs and metabolises Hb
What causes splenomegaly
Haemolytic anaemia
Infiltration by leukaemias and lymphomas
Accumulation of waste products of metabolism
Infections like malaria, schistosomiasis, HIV, glandular fever due to EBV
Chronic myeloid leukaemia
Myelofibrosis
Liver cirrhosis with portal hypertension
Myeloproliferative disorders
What is generally the aetiology behind splenomegaly
Typically due to increased workload
What risks are there with hyposplenism or having a splenectomy
Overwhelming sepsis
Infection by encapsulated bacteria
What are the causes of hyposplenism
Underlying disease causing destruction of spleen tissue - sickle-cell disease, coeliac disease
Splenectomy
What would you seen in the blood film of a patient with hyposplenism and why
Howell-Jolly bodies - DNA remnants in circulating erythrocytes
These are present as they are not removed due to the hyposplenism
What is the RES
The reticuloendothelial system
A network of cell located throughout the body and is part of a larger immune system
Role is to remove dead or damaged cells and identify and destroy foreign antigens in the blood
What function does the spleen have in the RES
Filters blood to remove damaged and old cells from circulation
Hb is removed from senescent erythrocytes and recylced with the globin portion being degraded to amino acids and haem portion metabolised to bilirubin
Describe the process by which bilirubin is removed from the body
Bilirubin is conjugated in the liver and secreted in bile
Bacteria in colon deconjugate and metabolise bilirubin into urobilinogen which is oxidised to form urobilin and stercobilin
Small amount of urobilinogen is reabsorbed and processed by kidneys to give yellow colour
What is the term for a low number of blood cells
Cytopenia
What is the term for a low number of red cells
Anaemia
What is the term for a low number of white cells
Leucopenia
What is the term for a low number of neutrophils
Neutropenia
What is the term for a low number of platelets
Thrombocytopenia
What is the term for a low number of RBCs, WBCs and platelets
Pancytopenia
What endings denote an increase in the number of cells
…cytosis or …philia
What is hypersplenism
Low blood count due to pooling of blood in an enlarged spleen
What controls neutrophil development and what does it do
G-CSF hormone which causes:
- Increased neutrophil production
- Decreased time to release mature neutrophils
- Enhanced chemotaxis
- Enhanced phagocytosis and pathogen destruction
What are the causes of neutrophilia
Actue inflammation
Haemorrhage
Smoking
Cancer
Tissue damage
Drugs
Cytokines
Metabolic/endocrine disorders
Myeloproliferative diseases
What are the causes of neutropenia
Increased removal/use - splenic pooling, sepsis, immune destruction
Benign ethnic neutropenia
Cyclic netropenia
Reduced production - B12/folate deficiency, infiltration of bone marrow by malignancy/fibrosis, aplastic anaemia, drugs, viral infections, congenital disorders
What are the potential consequences of neutropenia
Severe bacterial/fungal infection
Mucosal ulceration
Neutropenic sepsis
What are the causes of monocytosis
Chronic inflammatory conditions
Chronic infections
Carcinoma
Myeloproliferative disorders
What are the causes of eosinophilia
Allergic diseases
Drug hypersensitivity
Parasite infection
Acute lymphoblastic leukaemia, acute myeloid leukaemia, eosinophilic leukaemia
Hodgkin lymphoma
Myeloproliferative disorders
What are the causes of basophilia
Immediate hypersensitivity reactions
RA
Ulcerative colitis
Myeloproliferative disorders - systemic mastocytosis
What are the causes of lymphocytosis
Viral infections (especially in children)
Bacterail infections
Stress related
Post splenectomy
Smoking
Lymphoproliferative disorders - chronic lymphocyte leukaemia, lymphoma
