Haemopoiesis Flashcards
Where are blood cells produced? What is the difference in the distribution of this organ in childhood and adulthood?
Bone marrow (by progenitor stem cells - haemocytoblasts)
Child: extensive distribution (need to produce a lot of RBCs in a small amount of bone)
Adult: limited distribution (central only e.g. pelvis, sternum, skull, ribs, vertebrae)
What are the survival times for red blood cells, platelets, neutrophils, and lymphocytes?
Red blood cells = 120 days
Platelets = 10 days
Neutrophils = 2-4 days
Lymphocytes = 1 days (apart from memory cells - years)
Which cytokines stimulate the development of what blood cells?
Erythropoietin = stimulate RBC production
Thrombopoietin = stimulate platelet production
Granulocyte-colony stimulating factor = stimulate basophil & neutrophil production
Granulocyte-macrophage colony stimulating factor = stimulate neutrophils, eosinophils, basophils, monocytes, and erythrocytes
Interleukins = stimulate lymphoid cells
Tumour necrosis factor = causes apoptosis of tumours
How and where do you biopsy bone marrow?
Trephine biopsy
Take core from iliac crest
How can you measure RBCs?
Red cell count
Haemoglobin
Mean corpuscular volume (size of each RBC)
Outline the formation of different myeloid blood cells.
Myeloid progenitor —> Mast cells, Erythrocyte, Megakaryocyte, Myeloblast
Megakaryocyte —> Thrombocytes
Myeloblast —> Basophils, Neutrophils, Eosinophils, Monocytes
Monocyte —> Macrophage
Outline the formation of lymphoid blood cells.
Lymphoid progenitor cells —> Small lymphocytes, Natural killer cells
Small lymphocyte —> B-lymphocytes, T-lymphocytes
B-lymphocyte —> Plasma cells
T-lymphocyte —> CD4+ helper cells, CD8+ suppressor cells
Describe the important structural features of erythrocytes.
Biconcave disc
Globin chains protect haem molecule from oxidation, confer solubility, and permit variation in O2 affinity (by allowing a change in conformation)
Ankyrin anchors spectrin to cell membrane
+ actin & adducin & bands 3 and 4.1 & glycophorin
Describe the functions of erythrocytes.
- Deliver O2 to all tissues and CO2 to the lungs
- Carry Hb
- Maintain Hb in its reduced state
- Maintain osmotic equilibrium
- Generate ATP (for O2 exchange)
Give an example of a RBC disorder caused by defects in the cytoskeleton of the RBC membrane.
Hereditary spherocytosis = depletion of spectrin (~50%) —> rounded cells less resistant to lysis —> haemolysis —> haemolytic anaemia
(most commonly due to ankyrin defect)
Hereditary elliptocytosis = spectrin unable to form heterotetramers —> fragile ellipsoid cells —> haemolytic anaemia
What metabolic pathways can take place in RBCs?
- glucose metabolised to lactate (generates ATP) (as no mitochondria are present)
- G-6-P metabolised to generate NADPH (protection against reactive oxygen species/prevents Heinz bodies formation)
How is erythropoiesis regulated?
Interstitial peritubular kidney cells detect low pO2
Increase in erythropoietin synthesis
Increase in maturation and release of RBCs from bone marrow
Increase in haemoglobin
Increase in pO2
Decrease in erythropoietin synthesis
How is haemoglobin metabolised?
Haem —> Bilirubin (liver)
Bilirubin —> Gall bladder —> Bile duct —> Small intestine —> Large intestine —> Stercobilin
Bilirubin —> Kidney —> Urobilinogen
How are platelets formed?
Megakaryocytes produce platelets (cell fragments, therefore no nucleus) by increasing in cell size and replicating DNA, and platelets then bud from the cytoplasm.
Thromopoietin controls platelet production
Most platelets stored in spleen
What are the functions of platelets?
- adhesion to connective tissue
- aggregation with other platelets (hence keep agitated when stored)
- phospholipid membrane forms Ca2+ bridges with Gla domains of clotting factors
What are the three main components of platelet structure?
Alpha granules (glycoproteins) Glycoprotein receptors (help clotting factors and other platelets bind to the phospholipid membrane) Dense bodies
Summarise platelet adhesion and aggregation to damaged vessel walls.
Damage to vessel wall —> exposure of von Willebrand’s factor receptor —> platelets adhere (platelet plug)
Release of ADP from granules —> glycoprotein receptors exposed —> aggregation of platelets/clotting factors
Outline the action of neutrophils at wound sites.
Neutrophils adhere to blood vessel wall near to damaged cell when stimulated by activating substances released from bacteria and damages tissues
Neutrophils cross the plasma membrane by diapedesis when stimulated by histamine (sign of inflammation)
Neutrophil phagocytoses bacteria that have entered the wound site, and digests the bacteria using lysozymes
What is the reticuloendothelial system?
Immune system containing phagocytic cells (e.g. monocytes, macrophages, Kupffer cells, microglial cells, histiocytes) which identify and mount an appropriate immune response to foreign antibodies
Blood —> spleen & liver
ECF —> lymphatic system —> lymph nodes
When are different myeloid cells active?
Neutrophils = active in bacterial infection
Eosinophils = mediate hypersensitivity reactions e.g. asthma, skin inflammation
Basophils = allergic reactions
Outline the function of B-lymphocytes.
Humoral immunity = action of antibodies against antigens in the tissues
Express antigen-specific immunoglobulins and transform into plasmablasts (become plasma cells in the bone marrow and produce immunoglobulins) or memory cells (by interacting with T-cells)
Outline the function of T-lymphocytes.
Cellular immunity = activation of phagocytes, T-lymphocytes, and cytokines in response to an antigen (no antibodies involved)
Migrate to thymus and undergo T-cell receptor rearrangement to recognise immunoglobulins
- CD4+ helper cells = induce proliferation of T & B cells and activate marophages
- CD8+ suppressor cells = cytotoxic activity and induces apoptosis
Outline the functions of natural killer cells.
Have membrane-receptors for antigen-antibody complexes presented to them by B-cells
Recognise self (histiocompatibility antigens) and kill non-self cell lines by lysis
Kill viruses and tumour cells
Part of innate immune system