Session 3 - Haemopoiesis Flashcards
Where are the haemopoietic stem cells?
Which two progenitor cells do they divide into?
Bone marrow
Common Lymphoid progenitor cell
Common Myeloid progenitor cell
Where does haemopoiesis begin in the embryo?
- Vaculature of the yolk sac
- shifts to embryonic liver by weeks 5-8 in development
Thrombopoiesis creates which cell?
Are these cells nucleated and how many sets of chromosomes do they have?
Platelets
No nucleus
Several sets of chromosomes- polypoid cells
Platelets are polypoid cells. What does this mean?
They have more than 2 sets of chromosomes
Platelets bud off from which cell?
What drives formation of this cell and from what?
megakaryocytes
(TPO) thrombopoietin
drives megakaryocyte formation from the common myeloid progenitor cell
Granulopoiesis forms which cells?
Which are the precursor cells?
basophil eosinophil neutrophil
(‘fill’ with granules)
- Common myeloid progenitor cell
- Myeloblast
When do you see eosinophils in the blood?
Can they phagocytose?
Parasite infection or inappropriately with athsma/ allergy
Yes
How do macrophages protect tissues from pathogens?
Which cells do they derive from?
- phagocytosis
- secrete cytokines
- antigen presentation
Monocytes
(circulate in blood for >3 days)
B and T cells are formed by which process?
How does a B cell mature fully?
Where do the lymphocytes form?
Lymphopoiesis
Exposure to antigen in the lymphocytes which stimulates differentiation into a plasma or memory B cell.
Foetal liver and bone marrow/ thymus
How are the lymphocytes able to recognise so many different antigens?
Rearrangement of the receptor genes
- generates many different receptors each complementary to different antigens
How are common myeloid progenitor cells committed to the erythroid linkage?
What drives development into RBC’s once committed?
expression of transcription factors
- GATA1
- FOG1
- PU.1
EPO, erythropoietin
What stimulates more erythropoietin production?
What type of hormone is it?
What does EPO do?
hypoxia in the blood
glycoprotein hormone
- Protects erythroid cell line from apoptosis (inhibits)
by activating the EPO receptor - Drives RBC formation
How do erythroblasts become mature red blood cells?
- (nucleated) extrude the nucleus and most organelles to form reticulocytes
- Reticulocytes enter circulation
- Extrude remaining organelles, mitochondria and ribosomes
- Become mature RBC’s over 1-2 days
What is measured in the blood to estimate the amount of erythropoiesis occurring?
Explain
Reticulocyte count
Reticulocytes are immature RBC’s and mature quickly (1-2 days). So a low count would indicate no new erythropoiesis is occurring
Why are red blood cells particularly susceptible to oxidative damage?
They have no nucleus so can’t repair damaged proteins
Which cells are affected in pyruvate kinase deficiency?
Explain
Red blood cells
Pyruvate kinase is the last enzyme in glycolysis; it forms pyruvate. All products after the enzyme are reduced (ATP, pyruvate)
The red blood cell has no mitochondria so is reliant on glycolysis as the sole source of ATP.
Why are RBC’s biconcave?
- Optimises the laminar flow properties of blood in large vessels
- deformability through small capillaries
What do RBC’s do?
Exchange gases at the alveoli (O2 & CO2)
What causes hereditary spherocytosis?
Which defect is most common?
Mutations in the genes coding for membrane proteins (ankyrin, spectrin, band 3 protein and protein 4.2) which interact with the cytoskeleton to maintain the biconcave shape of RBC’s
Spectrin mutation
What happens in hereditary spherocytosis?
How can you treat it?
- The RBC’s are sphere shaped instead of biconcave.
- They are prone to lyse because they can’t deform in capillaries- causing haemolytic anaemia.
- They are cleared by the spleen
Splenectomy to reduce the anaemia
Adult haemoglobin has which subunits?
Each subunit is associated with what?
Hameoglobin A - tetramer
alpha2 beta2
A haem group which has Fe2+ at the centre of the porphyrin ring
Hameoglobin takes up how much of the RBC volume?
95%
What is the Bohr effect?
The binding affinity of haemoglobin (for oxygen) is inversely related to CO2 and pH
2, 3 Bisphosphoglycerate
(2, 3 BPG) has what effect on oxygen binding to haemoglobin?
Why?
Reduces affinity for oxygen
BPG is an intermediate of glycolysis so its presence indicates a respiring tissue which needs oxygen
How does the oxygen dissociation curve shift if haemoglobin’s affinity for oxygen is reduced?
What shape is the curve?
Shifts right
- the haemoglobin is less saturated at the same partial pressures
sigmoidal (s shaped)
What does the red and white pulp of the spleen do?
Red pulp - removes RBC’s and metabolises haemoglobin
White pulp- synthesises antibodies, removes antibody-coated bacteria and blood cells
Which cells pass through the red and white pulp preferentially?
What is each pulp made up of?
red- erythrocytes
white- WBC’s and plasma
Red - sinuses lined with endothelial macrophages and cords
White- structure similar to lymphoid follicles
(sinuses= collecting ducts which lead to internal veins)
The spleen can pool blood, what is the advantage?
Platelets and red cells can be rapidly mobilised from here during bleeding
What can cause splenomegaly?
- Increased workload- haemolytic anaemia
- Congestion (can’t empty) due to portal hypertension
Note; portal vein drains blood from intestines and spleen to the liver) - Infiltration by leukaemia and lymphomas
- expansion due to accumulation of waste products of metabolism. E.g. Gaucher’s disease
- infectious disease; HIV, glandular fever, malaria, schistosomiasis
What is Gaucher’s disease?
What does it present like?
- Accumulation of glucocerebroside (component of red and white blood cell membranes) in fibrils
- Due to a defect in the beta-glucosidase enzyme
splenomegaly
Which infectious disease can cause splenomegaly?
HIV
Malaria
Glandular fever
Schistosomiasis
What is hyposplenism?
What is it caused by and what are the risks?
Reduced splenic function
- Trauma causing splenic rupture
- Damaged tissue in disease; coeliac, sickle cell
- Splenectomy
Risk of sepsis
What is present in the blood film of a patient with hyposplenism?
Explain
Howell-Jolly Bodies in RBC’s
They’re nuclear remnants which are normally expelled from maturing RBC’s. The spleen would usually remove them so it indicates reduced function
Which cells make up the reticuloendothelial system?
macrophages and monocytes
Where are these cells found?
- Kupffer cell
- Tissue histiocyte
- Microglia
- Langerhans cell
They are all types of ___?
liver
connective tissue
CNS
skin & mucosa
Macrophage
What is haemoglobin metabolised to?
(in spleen)
globin > amino acids
haem > bilirubin
Urobilinogen
Urobilin & stercobilin
What do they do?
Where do they come from?
- Give urine its colour *
- Give stool its colour
- Bilirubin is excreted in bile into the duodenum
- Colon bacteria oxidise it to urobilinogen
- Further oxidised to urobilin and stercobilin
