1.1 Erythropoiesis and Anaemia Flashcards
What are the definitions of hematopoiesis and erythropoiesis?
Hematopoiesis = generation of blood cells (hematopoietic stem cells) predominantly in bone marrow
Erythropoiesis = formation of red blood cells (erythrocytes) from HSC
What is myelopoiesis and thrombopoiesis?
Myelopoiesis = formation of white blood cells
Thrombopoiesis = formation of platelets (clotting)
What is the general progression of erythropoiesis?
- Haematopoietic stem cells differentiate into erythroblasts
- Erythoblasts loose some organelles and nuclei and mature into reticulocytes
- Reticulocytes loose remaining organelles and mature into erythrocytes (RBC) with no nucleus
What is the lifespan of red blood cells, white blood cells, and platelets?
RBC = about 120 days
WBC = vary between hours and years
Platelets = 7 - 10 days
Where does hematopoiesis occur?
Predominantly in the bone marrow
Alternate sources when foetus (egg sac, liver, spleen)
Progenitors make up the first phase of erythropoiesis. What key changes occur during this phase?
- Hematopoietic stem cells (HSC) become Bust-Forming Unit Erythroids (BFU-E)
- BFU-E cells differentiate into Colony Forming Unit Erythroids (CFU-E)
- CFU-E eventually become Proerythoblasts
What is the significance of Bust-Forming Unit Erythroids (BFU-E)?
First progenitors committed solely to the erythroid lineage
Precursors (ranging from proerythroblasts to reticulocytes) make up the second phase of erythropoiesis. What are the changes that occur during the 7 days of this phase?
- Proerythroblasts > Basophilic erythroblasts
- Basophilic erythoblasts > Polychromatophilic erythoblasts
- Polychromatic erythoblasts > Orthochromatic erythroblasts
- Orthochromatic erythoblasts > Reticulocytes
Maturation marks the final phase of erythropoiesis. How is this process undergone?
- Reticulocytes move from bone marrow into peripheral blood
- Final maturation = repeated passage through spleen/marrow into blood circulation (48hrs) = strained until mature into RBC
What are the key differences of reticulocytes and erythrocytes?
Reticulocytes = No nucleus, reduced size, some RNA
Erthrocytes = Mature RBC = No DNA, no RNA, cannot synthesis Hb
What are erythroblastic islands?
A central macrophage (WBC) surrounded by up to 30 erthroid cells of varying degrees of maturation
What is the purpose of erythoblastic islands?
Anchors erythoblasts + drives differentiation via phagocytosis of extruded nucelus
Haemoglobin synthesis via transfer of iron
What is haemoglobin synthesis / biosynthesis in erythropoiesis?
Occurs 2nd phase
Binds heme to developing erythrocytes
Heme = iron rich and 35% of RBC volume, gives colour + oxygen binding
Erythropoietin (EPO) is a hormone secreted by kidneys to regulate RBC production. How is this done?
Oxygen regulates EPOs (less oxygen = more EPO produced = more RBC for oxgen transport increase)
EPO binds to receptors on erythroblasts (CFU-E) which stimulate proliferation of erythroid precursors (STAT5 signalling)
What is the complete life cycle of a an erythrocyte?
- Haematopoietic stem cells develop into reticuolcytes in bone marrow
- Reticulocytes move into blood stream and mature into erythrocytes and criculate for 120 days
- Once old or damaged, they are phagocytised in bone marrow, liver, and spleen
What happens when an erythrocyte is phagocytised?
Lysosomes break down the cell components and the globin portion of Hb is metabolised into amino acids and recycled
Globin, amino acids, and cell components return to hematopoietic bone marrow to be used in haematopoiesis again
After globin is removed from Hb, the remainder is split into heme groups and iron ions. What happens to these?
Heme groups = broken down to biliberdin and either recycled for haematopoiesis or used as bilirubin in the liver
Iron ions = bound to transferrin and either recycled for haematopoiesis or stored in the liver as ferritin
What is anaemia?
When erythopoiesis goes wrong = deficiency in number or quality of RBCs
What are some causes of anaemia?
Deficient production of RBCs
Excesive destruction of RBCs
Blood loss or haemorrhaging
What are 4 different presentations of anaemia?
- Hypochromatic = ion deficiency, thalassemia
- Microcytic = smaller RBCs, can also be hypochromic, ion deficiency
- Macrocytic = RBCs are larger than normal
- Normocytic = Normal RBCs, but fewer of them
Iron deficiency anaemia is responsible for 50% of all anaemia. What is the presentation of iron deficiency anaemia?
Presentation = hypochromic and microcytic
What are the causes of iron deficiency anaemia?
- Increased iron requirements (growth demands)
- Lmiited external supply of iron (malabsorption)
- Blood loss
What is the presentation and causes of microcytic anaemia?
Blood smear = small, often hypochromic RBCs
Mean corpuscular volume (MCV) is low
MCV = <70fL (normal = 80-90fL)
What are the causes of microcytic anaemia?
- Iron deficiency
- Thalassaemia (genetic disorder resulting in abnormal Hb)
Only 3-6% of adults habe macrocytic anaemia. What is the presentation of this rare form of anaemia?
Unusually large RBCs
MCV (mean copuscular volume) is high, >100fL
What are the causes of macrocytic anaemia?
Insufficient uptake or absroption of vitamin B12 (eg pernicious anaemia or redcued gastric acid)
Alcoholism
What is the presentation of normocytic anaemia?
Normal RBC size and Hb content, but fewer present
What are the causes of normocytic anaemia?
Decreased production (eg from chronic disease)
Increased destruction / loss (eg acute bleeding or hyper splenism)
Increased plasma volume (eg pregnancy)
What are the clinical signs and symtpoms of anaemia?
Signs = tiredness, dizziness, palpitation, headache
Symptoms = jaundice (yellow skin/membrane) and koilonychia (spoon nails)
What are the oral manifestations of anaemia?
- Pallor of mucous membrane
- Atrophic glossitis (smooth/gloosy appearance)
- Angular cheilitis (inflamed and cracked skin at angle of mouth eg iron deficiency)
