Session 3: Haemopoeisis, Spleen and Bone Marrow Flashcards
Where does haemopoiesis take place?
The sole site of haemopoiesis is in the bone marrow.
Where does haemopoiesis take place in infants and children?
In bone marrow throughout the body.
Where does haemopoiesis take place in adults predominantly?
In the pelvis, sternum, skill, ribs and vertebrae.
A blood cells derive from a single common precursor. Which?
The multipotential haematopoietic stem cell also called a haemocytoblast.
Explain the lineage of thrombocytes (platelets).
HSC differentiates into a common myeloid progenitor. This progenitor in its turn is turned into a megakaryocyte which then forms platelets.
Which growth factor is thrombopoiesis dependent on?
Thrombopoietin
Which are the granulocytes?
Basophils, neutrophils and eosinophils.
Explain the lineage of granulopoiesis.
HSC -> common myeloid progenitor -> Myeloblast.
Which growth factor is granulopoiesis dependent on?
G-CSF.
What are neutrophils mainly involved in?
Migration to areas of inflammation by chemotaxis to phagocytose invading microbes and destroy them by respiratory burst.
What are eosinophils mainly involved in?
Phagocytosis of multicellular parasites such as helminths in response to the immune system.
What is inappropriate activation of eosinophils associated with?
Asthma and allergy.
What are basophils mainly involved in?
Plays a role in parasitic infections and allergy.
What are monocytes?
Monocytes circulate in the blood for 1-3 days before moving into tissues where they differentiate into macrophages or dendritic cells. Monocytes in the blood can also perform phagocytosis after recognising antibodies or complement that coats pathogens. Also by binding directly via pattern-recognition receptors that recognise pathogens.
Explain monocytopoiesis.
HSC -> CMP -> Myeloblast -> Monocyte
Where can B and T lymphocytes be found?
They can be found in blood but most commonly they are found in the lymphatic system.
Where does development of B lymphocytes occur?
In the fetal liver and bone marrow.
Where does development of T lymphocytes occur?
In the fetal liver and later on moves on to the thymus early in gestation.
How does maturation of B lymphocytes occur?
It requires exposure to antigen in the lymph nodes. They can now recognise non-self antigens and produce large quantities of antibodies.
How do T lymphocytes differ to B lymphocytes?
T lymphocytes recognise a wide range of antigens that are presented to them by antigen-presenting cells. Meaning T lymphocytes needs the antigens presented to them. B lymphocytes do not.
Explain the lymphocyte lineage.
HSC -> Common lymphoid progenitor -> small lymphocyte -> and then either to B lymphocytes or T lymphocytes. Growth factors include Its and TNFs.
Explain erythropoiesis.
HSC -> CMP -> Erythrocyte by growth factor erythropoietin.
Where does erythropoiesis take place?
In the bone marrow.
What is the life span of a red blood cell?
Around 120 days.
What is erythropoietin released by?
The kidneys.
What is erythropoietin production increased by?
As a response to a decreased oxygen level in the blood (hypoxia).
What is erythropoietin’s main function?
To inhibit apoptosis of progenitor cells of RBCs. Activation of erythropoietin cells on these progenitors allows them to develop, differentiate and proliferate. During this process RBCs extrude their nucleus and most of their organelles.
What is an immature red blood cell called?
Reticulocyte.
How long does it take for a reticulocyte to become a red blood cell?
Around 1-2 days.
Why is a reticulocyte count good to do?
IT provides a good diagnostic estimate o the amount of erythropoiesis occurring in a patient’s blood marrow.
Why are red blood cells susceptible to damage in G6PD deficiency?
Because they lack nuclei they are unable to replace damaged proteins by re-synthesis. This means that the increased oxidative damage that occurs due to G6PD deficiency and NADPH deficiency red blood cells are more prone to damage.
Why are red blood cells susceptible to damage in pyruvate kinase deficiency?
Because the lack of mitochondria means that red blood cells rely on glycolysis for their energy production.
Explain the structure of red blood cells.
Anucleated biconcave discs.
Explain the structure of the cell membrane of an erythrocyte.
The lipid bilayer contains proteins such as spectrin, ankyrin, band 3 and protein 4.2. These proteins contribute to the cytoskeleton and structure of the RBCs.
What happens if there would be a mutation of the genes expressing those membrane associated proteins?
It can result in hereditary spherocytosis or hereditary elliptocytosis.
What is the structure of the adult haemoglobin?
Two alpha sub units and two beta subunits.
What decreases the affinity of haemoglobin to oxygen?
An increase in BPG, CO2, temperature or a decrease in pH.
What are some sources of haemopoietic stem cells?
Aspiration of bone marrow (not very common)
GCSF mobilised stem cells in the peripheral blood.
Umbilical cord stem cells acquired at time of a normal delivery.
Where can the spleen be found?
The left upper quadrant of the abdomen.
What does the spleen consist of?
Red pulp and white pulp.
Explain how blood enters the spleen and where it goes.
It enters via the splenic artery.
White cells and plasma pass through the white pulp.
Red blood cells pass through the red pulp.
What is the function and structure of the red pulp?
To remove old red cells and metabolise haemoglobin.
Sinuses lined by endothelial macrophages and cords.
What is the function and structure of the white pulp?
Synthesis of antibodies and remove antibody-coated bacteria and blood cells.
Similar structure to lymphoid follicles.
What are the general functions of the spleen?
Removal of red cells by macrophages.
Synthesis of antibodies and removal of antibody coated bacteria.
Immunological function where 25% of T-cells and 15% of B-cells are found in the spleen.
Blood pooling.
Extramedullary haemopoiesis.
What is blood pooling?
Platelets and red blood cells can be rapidly mobilised during bleeding.
What is extra medullary haemopoiesis?
Pluripotential stem cells proliferate during haematological stress or if the marrow fails.
Why is it important to counsel people who have had their spleens removed?
Because of the increased risk of sepsis.
What is splenomegaly?
An enlarged spleen.
Give some causes of splenomegaly.
Increased workload such as:
Haemolytic anaemia where an increased number of defective red cells are removed.
Portal hypertension
Infiltration by leukaemias and lymphomas.
Accumulation of waste products of metabolism.
Overworking either red or white pulp.
Gaucher’s disease or sarcoidosis.
Infectious disease such as malaria, HIV and glandual fever by Epstein Barr Virus.
What is hyposplenism?
A term used to describe reduced splenic function.
What are patients with hyposplenism at an increased risk of?
Sepsis.
What are some causes of hyposplenism?
Disease which destroy spleen tissue such as sickle-cell disease and coeliac disease as well as splenectomy.
What are Howell-Jolly bodies?
Basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes.
How do Howell-Jolly bodies come about?
During erythropoiesis RBCs normally expels their nuclei but in some cases a small portion of DNA remains inside.
A blood film from a patient can reveal Howell-Jolly bodies. Why would you take a blood film to see if there are Howell-Jolly bodies present?
Usually the RBCs with Howell-Jolly bodies are removed by the spleen in a healthy person. However the presence of Howell-Jolly bodies is a good indicator of hyposplenism and hence reduced splenic function.
What is the reticuloendothelial system?
A network of cells located throughout the body that is part of the larger immune system.
The role is to remove dead or damaged cells and to identify and destroy foreign antigens in blood and tissues.
What cells can be found in the reticuloendothelial system?
Phagocytic cells, include monocytes and different types of macrophages.
What macrophage types can be found in the following:
- Liver
- Connective tissue
- CNS
- Peritoneal cavity
- Spleen
- Skin and mucosa
- Kupffer cells
- Tissue histiocytes
- Microglia
- Peritoneal macrophages
- Red pulp macrophages
- Langerhans cells
Explain the breakdown of haemoglobin.
Recycled by the spleen and broken down into haem portion and globin portion.
What is the fate of the globin portion?
It is broken down into its constitutive amino acids.
What is the fate of the haem portion?
Metabolised to bilirubin which is the removed in the liver where it is conjugated and secreted in bile.
What happens to bilirubin in the colon?
Bacteria deconjugate and metabolise bilirubin into colourless urobilinogen. This is the oxidised into urobilin and stercobilin.
What are causes of massive splenomegaly?
Chronic myeloid leukaemia
Myelofibrosis
Malaria
Schistosomiasis
What are causes of moderate splenomegaly?
Same as massive but also: Lymphoma Leukaemias Myeloproliferative disordes Liver cirrhosis Portal hypertension Infections such as glandular fever by Epstein Barr virus
What are causes of mild splenomegaly?
Same as massive and moderate as well as:
Hepatitis
Endocarditis
Infiltrative disorder such as sarcoidosis
Explain how the body responds to becoming anaemic.
A reduced pO2 is detected in the interstitial peritubular cells in the kidney.
This increases the production of erythropoietin by the kidneys.
Erythropoietin stimulates maturation and released of RBCs from the bone marrow.
The number of red cells increase and so does haemoglobin.
More oxygen can be delivered.
Define cytopenia.
A reduction in the number of blood cells.
Give examples of types of cytopenias.
Anaemia Leucopenia Neutropenia Thrombocytopenia Pancytopenia (reduction in all three lines)
Define cytosis or cytophilia.
An increase in the number of blood cells.
Give expamples of cytosis/cytophilia.
Erythrocytosis Leucocytosis Neutrophilia Lymphocytosis Thrombocytosis
What are the most common causes of an increase in neutrophils?
Infections
Acute inflammation
Tissue damage.
Give some causes of neutropenia.
B12/folate deficiency. Hyposplenism Aplastic anaemia Radiation Drugs Viral infection Congenital disorders
