Haemopoeisis, the spleen and bone marrow blood counts and films Flashcards
session 6:
what is haempoeisis and describe its origin and where it takes place.
Haemopoiesis is the process by which blood cells are formed. Haemopoeisis involves the specification of blood lineages and the proliferation to maintain an adequate number of cells in the circulation.
In an early embryo this process begins in the vasculature of the yolk sac before shifting to the embryonic liver by week 5-8 gestation.
After birth the sole site of haemopoeisis is in the bone marrow. the main sites in adult marrow are the pelvis the sternum, skull, ribs and vertabrae.
five major lineage pathways that arise from the haemopoetic stem cells in bone marrow
1- Thrombopoesis - formation of platelets( thrombocytes) from megakaryocytic
2- Monocytopoesis- precursor to macrophages and dendritic cells, from the myeloblast which is from the common myeloid progenitor.
3- Granulopoesis- results in basophil, neutrophil and eosinophil
4- Lymphopoeisis- B and T lymphocytes from the small lymphocyte which is derived from the common lymphoid progenitor.
5- Erythropoeisis- continual production of red blood cells
structure and function of thrombocytes
Structure:
Complex surface cell membrane with a cytoplasm that contains alpha granules that have fibrinogen, von willebrand factor and other large molecules and dense granules that contain small molecules like ADP and calcium.
Function:
to assist in the coagulation or thrombosis of blood. platelets are rich in serotonin(causes the constriction of blood wall vessels) and phospholipid factor III, which activates prothrombin into thrombin which converts soluble fibrinogen into insoluble fibrin to form the blood clot. this is an example of an enzyme cascade and proteolytic activation.
describe the function of granulocytes
the granuloctyes are basophils, neutrophils and eosinophils, they arise from myeloblast cells which arose from common myeloid progenitor cells.
mature neutrophils migrate to areas of inflammation by chemotaxis where they phagocytose invading microbes and destroy them by respiratory burst ( rapid production of superoxide and H2O2).
Eosinophils have a similar ability and are associated with immune responses to multicellular parasites.
- inappropriate activation of eosinophils is associated with asthma and allergy.
Basophils are the least common and have a role to play in immune response to parasitic infection and allergy.
Describe the function of Monocytes
monocytes are the precursor for macrophages(phagocytosis) and dendritic cells(adaptive immunity via activation of T cells) , they circulate for 1-3 days prior to differentiation. they can perform phagocytosis after recognising antibodies or complement that coats pathogens or by binding direct via pattern recognition receptors that recognise pathogens.
macrophages protect tissues via phagocytosis , antigen presentation and cytokine production.
function of Lymphocytes
B and T lymphocytes principally belong in the lymphatic system.
t - the progenitors arise from fetal liver and migrate to the thymus early in gestation.
Immature T cells undergo rearrangement of the T cell receptor genes resulting in the ability to produce a cast array of different T cell receptors which can recognise a wide range of antigens presented to them by antigen presenting cells ( dendritic cells ).
B- cell development commences in the fetal liver and bone marrow and during their development immuniglobin genes rearrange to allow production widely specified antibodies.
final maturation of B cells requires exposure to antigens in the lymph nodes leading to B cells that can recognise non self antigens and produce large amounts of antibodies.
function of erythrocytes.
RBC’s have a final lifespan of 120 days in the blood and cannot divide.
they are made due to the action of transcription factors GATA1, FOG1 and PU1 on erythroblasts. expansion of the erythroid precursor erythroblasts is triggered by the hormone Erythropoietin in the adult kidney. it stimulates their survival, proliferation and differentiation into reticulocytes.
EPO is triggered by low blood oxygen ( hypoxia ).
Explain the significance of the reticulocyte count
the reticulocyte count is a good diagnostic estimate of the amount of erythropoeisis occurring in a patients bone marrow.
what diseases are red blood cells particularly susceptible to.
mature erythrocytes do not have nuclei meaning they are unable to replace damaged proteins by re-synthesis so they are particularly susceptible to oxidative damage in diseases like glucose-6-phosphate dehydrogenase deficiency.
they rely on glycolysis for energy production as they do not have mitochondria thus pyruvate kinase deficiency has very significant consequences.
how much of the blood is made by erythrocytes
40-50%
Describe the role of the spleen
- Understand the causes and clinical significance of splenomegaly
splenomegaly is the enlargement of the spleen.
causes are:
hypersplenism(overactive spleen) - associated with haemolytic anaemia.
congestion due to portal hypertension,
infiltration by leukaemia and lymphomas
expansion due to accumulation of water products of metabolism.
some infectious diseases can be characterised by splenomegaly, most notably malaria, schistosomiasis, HIV and glandular fever caused by Epstein Barr Virus.
- Understand the causes and clinical significance of hyposplenism
hyposplenism is reduced splenic function and is associated with increased risk of overwhelming sepsis.
causes:
underlying diseases which destroy spleen tissue like HbS and coeliac disease.
splenectomy - usually due to rupture from trauma and because of cancer. \
blood from a patient with hyposplenism will typically reveal Howell Jolly bodies( remnants of RBC nuclei normally removed in the spleen) - an indicator that the spleen isn’t working well.
where is the spleen located
in the left upper quadrant of the abdomen
what is the role of the spleen
the spleen has a key role in the reticuloendothelial system filtering blood to remove deformed and old cells from the circulation. acts as a blood filter. blood enters through the splenic artery.
red cells preferentially pass through the Red pulp ( sinuses lined by endothelial macrophages and cords) remove old red cells and metabolises the haemoglobin.
white cells and plasma preferentially pass through white pulp( has a similar structure to lymphoid follicles) where anybody synthesis and antibody coated bacteria and blood cell removal occurs.
the spleen also has a blood pooling function from which platelets and red cells can be rapidly mobilised during bleeding.
what happens to haemoglobin when it is recycled by the spleen
Haemoglobin removed from senescent erythrocytes is recycled with the globin being reduced to amino acids and the haem being meabolised to bilirubin which is removed in the liver and secreted with bile.
bacteria in the intestines deconjugate bilirubin into colourless urobilinogen which is oxidised to from stercobillin( responsible for the brown colour of faeces)
a small amount urobilinogen is reabsorbed and processed by the kidneys to be oxides to urobiliin( gives urin the yellow colour)
