Red Blood Cells Flashcards
Where do all blood cells orginate?
Bone marrow
Which type of cells are the precursor of all blood cells?
Haemopoietic stem cells
Which 2 cell types do pluripotent haemopoietic stem cells give rise to?
- Lymphoid progenitor cells
- Myeloid progenitor cells
What 3 types of cells do common lymphoid progenitor cells differentiate into?
- T cells
- B cells —> plasma
- NK cells
What 4 types of cells do common myeloid progenitor cells differentiate into?
- Megakaryocytes —> platelets
- Erythrocytes
- Mast cells
- Myeloblasts
What 4 types of cells do myeloblasts differentiate into?
- Basophils
- Neutrophils
- Eosinophils
- Monocytes
What are the 3 types of granulocytes?
- Basophils
- Neutrophils
- Eosinophils
What are the 4 cell steps of platelet production?
- Haemopoietic stem cell
- Common myleoid progenitor cell
- Megakaryocyte
- Platelets
What are the 3 cell steps of erythrocyte production?
- Haemopoietic stem cell
- Common myleoid progenitor cell
- Erythrocytes
What are the 3 cell steps of mast cell production?
- Haemopoietic stem cell
- Common myleoid progenitor cell
- Mast cell
What are the 4 cell steps of basophil production?
- Haemopoietic stem cell
- Common myleoid progenitor cell
- Myeloblast
- Basophil
What are the 4 cell steps of neutrophil production?
- Haemopoietic stem cell
- Common myleoid progenitor cell
- Myeloblast
- Neutrophil
What are the 4 cell steps of eosinophil production?
- Haemopoietic stem cell
- Common myleoid progenitor cell
- Myeloblast
- Eosinophil
What are the 5 cell steps of macrophage production?
- Haemopoietic stem cell
- Common myleoid progenitor cell
- Myeloblast
- Monocyte
- Macrophage
What are the 3 cell steps of natural killer (NK) cell production?
- Haemopoietic stem cell
- Common lymphoid progenitor cell
- NK cell
What are the 4 cell steps of B lymphocyte production?
- Haemopoietic stem cell
- Common lymphoid progenitor cell
- Small lymphocyte
- B cell
What are the 4 cell steps of T lymphocyte production?
- Haemopoietic stem cell
- Common lymphoid progenitor cell
- Small lymphocyte
- T cell
What is the lifespan of an erythrocyte?
120 days
What are the 2 essential characteristics of HSCs?
- Self-renew
- Differentiate to mature progeny
What are the 3 sites of haemopoiesis and when are they used?
- Yolk sac - 3 weeks gestation
—> generate HSCs in mesoderm - Liver - 6-8 weeks genstation
- Bone marrow - 10 weeks gestation
- children —> all bones
- adults —> pelvis
—> vertebrae
—> sternum
What is the difference between the location of haemopoesis in children vs adults?
Children —> all bones
Adults —> femur, vertebrae, sternum
What are pluripotent HSCs surrounded by in bone marrow? (3)
- Mesenchymal cells
- Endothelial cells
- Vasculature
What can disruption of HSC regulation cause?
Unbalanced proliferation and differentiation
1. Leukaemia
2. Bone marrow failure
Which 4 factors regulate haemopoiesis?
- Genes
- Transcription factors
- Growth factors
- Microenvironment
What are haemopoietic growth factors?
Glycoprotein hormones
- Erythrocytes —> erythropoietin (EPO)
- Granulocytes and monocytes —> G-CSF
—> G-M CSF
—> cytokines
- Platelets —> thrombopoietin (TPO)
Where are haemopoietic growth factors produced?
Bone marrow except EPO (kidney)
Where are B, T and NK cell progenitors found?
- B —> bone marrow
- T —> thymus
- NK —> bone marrow
What do mature B cells produce for immunity?
Antibodies —> humoral immunity
What do mature T and NK cells produce for immunity?
Cytokines —> cellular immunity
What are the 4 steps of erythrocyte differentiation?
- Proerythroblast
- Erythroblast
- Reticulocyte
- Erythrocyte
Which stain is used to see erythroblasts and why?
New methylene blue
- stains RNA —> can see maturing as nucleus lost
What are reticulocytes and how are they identified on a blood film?
Immature erythrocyte
- circle with coloured dots —> RNA content
Which 4 nutrients/chemicals are a necessity for erythropoiesis?
- Iron
- Folic acid
- Vit B12
- EPO
What are small erythrocytes described as? (diameter)
Microcytic
- <6μm
- iron deficieny anaemia
- anaemia of chronic disease
What are large erythrocytes described as?
Macrocytic
- >9μm
- megaloblastic anaemia
What are 3 causes of iron deficiency?
- Blood loss
- Insufficient dietary intake
- Increased requirement
Which disease leads to decreased iron availability?
Anaemia of chronic disease/inflammation
Which 2 diseases can be identified by microcytic erythrocytes?
- Iron deficieny anaemia
- Anaemia of chronic disease
What disease does iron/vit B12/folic acid deficiency lead to?
Megaloblastic anaemia
Why does vit B12/folic acid deficiency create macrocytic erythrocytes?
Dec B12 and folate —> dec thymidine production —> dec DNA synthesis —> dec cell division (cells keep growing and don’t split)
What is the cause of megaloblastic anaemia?
B12 or folic acid deficiency
What stimulates erythropoietin production in the kidneys?
Hypoxia
What are the 2 major functions of iron?
- Hb oxygen transport
- Mitochondrial proteins
- cytochrome a, b, c —> ATP production
- cytochrome P450 —> hydroxylation
What are 3 symptoms of iron-deficiency anaemia?
- Koilonychia —> spoon shaped nails
- Glossitis —> inflammed tongue
- Angular stomatitis —> sores at mouth corners
+ hypochromic, macrocytic erythrocytes
What is the cause of iron-deficiency anaemia?
What is the average consumed vs absorbed mass of iron per day and why is there a difference?
10-20 mg/day —> 1-2 mg
What foods are high in iron?
Haem - animal-products
Non-haem - soya beans
What is haem iron?
Ferrous iron (Fe2+)
What is non-haem iron and what must be done to absorb it?
Ferric iron (Fe3+)
- must be reduced (eg. by vit C) to be absorbed
Why is consuming excess iron bad?
Toxic to heart and liver
- not excreted
Where is iron stored in the body? (5)
- Bone marrow
- Red blood cells
- Spleen
- Muscle
- Liver —> ferritin
How is iron lost during everyday life?
Skin shedding —> unregulated
In what form is iron transported round the body?
Transferrin in plasma
Which chemical inhibits iron absorption and storage?
Hepcidin
When is hepcidin secreted and where from?
Secreted from liver when iron storage levels are high
Where is iron absorbed from?
Duodenum
Which 4 pro-inflammatory cytokines inhibit erythropoietin production?
- IL-1
- TNFα
- IL-6
- IFNγ
Which 3 pro-inflammatory cytokines aid hepcidin production?
- IL-1
- TNFα
- IL-6
What are the 2 major functions of vit B12?
- DNA synthesis
- Nervous system
What are the 2 major functions of folic acid?
- DNA synthesis
- Homocysteine metabolism
Why are vit B12 and folic acid essential for DNA synthesis?
Needed for dTTP synthesis —> needed for thymidine synthesis
Why does a vit B12 or folic acid deficiency effect the bone marrow and how?
Effect all rapidly divinding cells (bone marrow, epithelial, gonads)
- megaloblastic erythropoiesis
What are sources of vit B12?
Animal products
- fish, crab, chicken, eggs, milk etc.
What are sources of folic acid?
Plant products
- citrus fruit, dark leafy greens, avocado, broccoli etc.
When do folic acid requirements increase?
- Pregnancy
- Increased erythrocyte production (eg. haemolytic
anaemias like sickle cell)
What are the 2 steps of vit B12 absorption?
- Stomach —> combines with IF from gastric parietal
cells - Small intestine —> B12-IF binds to ileum receptors
What are the 4 causes of vit B12 deficiency and why?
- Insufficient intake (eg. veganism)
- Pernicious anaemia —> autoimmune dec IF
- Malabsorption (eg. coeliac, surgery)
- Achlorhydria —> lack of stomach acid
Where are erythrocytes destroyed?
Spleen —> by splenic macrophages after 120 days
What happens to the haemoglobin of destroyed erythrocytes?
Haem —> bilirub - excreted in bile
—> iron back to bone marrow
Globin —> hydrolysed to amino acids
What does erythrocyte survival depend on? (3)
- Membrane integrity
- Haemoglobin
- Cellular metabolism
- issues —> haemolysis
What causes pernicious anaemia?
What is the shape of erythrocytes and why?
Biconcave discs
- no nucleus —> manoeuvre in small blood vessels
—> space for Hb to carry oxygen
- diameter: 7.5 µm
depth: 2 µm
What does damage to vertical linkages in erythrocyte membranes cause them to become and why?
Spherocytes
- vertical linkages (ankyrin/spectrin) damaged —> lose
membrane —> too much cytoplasm —> swell —>
spherocytes —> haemolysis
- cause —> hereditary spherocytosis (auto dom)
What does damage to horizontal linkages in erythrocyte membranes cause them to become?
Elliptocytes
- cause —> hereditary elliptocytosis
—> iron deficiency
Why is the PPP important to erythrocytes?
Mode 3 of PPP —> NADPH produced —> reduces glutathione —> reduced glutathione = vital antioxidant in erythrocytes
Why does G6PD deficiency affect erythrocytes?
Rate-limiting enzyme in PPP —> maintains NADPH reducing power
- G6PD deficiency —> less reduced glutathione —>
erythrocytes vulnerable to oxidant damage —>
severe intravascular haemolysis
Which disease does the distribution of G6PD deficiency parallel and why?
Malaria
- hostile environment
How can G6PD deficiency be identified on a blood film?
- Bite cells - oxidant damage to membrane and Hb
- Heinz bodies - Hb denatured
What is polycythaemia?
Too many erythrocytes
- blood hyperviscosity —> vascular obstruction
—> thrombosis
How is polycythaemia detected on a blood count?
- Hb inc
- RBC inc
- Hct inc
What are the 2 types of polycythaemia?
- Pseudo - dec plasma volume —> high conc of
erythrocytes - Vera - actually inc in erythrocytes
What causes pseudo-polycythaemia
Dec plasma volume
What are the 4 causes of vera-polycythaemia?
- Blood doping/ overtransfusion
- Hypoxia - inc altitude
- cardiac/respiratory disorders
—> inc EPO - Inappropriate EPO inc - renal tumour
- administered (athletes) - Myeloproliferation - bone marrow issue
What is a visible symptom of hypoxia?
Central cyanosis —> blue tongue/lips
How can polycythaemia be treated? (2)
- Venesection —> dec blood viscosity
- Drugs —> inhibit bone marrow erythropoiesis