HAEM - RBC Flashcards
Haemopoiesis
Blood cell type production which originate in the bone marrow
Lineage of cells
Derived from pluripotent haemopoietic stem cells
They give rise to lymphoid stem cells (forming lymphocytes)
OR
Myeloid stem cells (forming erythrocytes, platelets, monocytes, mast cells, eosinophils and basophils)
Erythrocyte
Intravascular life span - 120 days
Function - oxygen transport
Platelet
10 days
Haemostasis
Monocyte
Several days
Phagocytosis + killing of micro-organisms
Neutrophil
7-10 hours
Phagocytosis + killing of micro-organisms
Eosinophil
Lifespan shorter than 7-10 hours
Defence against parasitic infection
Lymphocyte
Very variable lifespan
Humoral/cellular immunity
Haemopoietic stem cells characteristics
1) They can self-renew - continuously provide more progenitors to differentiate further (pool of HSCs not depleted) - some daughter cells remain as HSC
2) Differentiate to mature progeny
After HSC comes
Common myeloid/lymphoid progenitors
Platelets are
Broken down from megakaryocytes
Sites of haemopoiesis 3 weeks
Yolk sac ; generation of HSC (mesoderm)
Mesoderm
Middle developmental layer giving rise to skeleton, muscle, heart and bones
Haemopoiesis 6-8 weeks
Liver takes over and principle source of blood in foetus until shortly after birth
Haemopoiesis 10 weeks gestation
Children - occurs in all bones’ marrow
Adults - mainly in bone marrow of the pelvis, vertebrae and sternum
HSC and progenitor
Distributed in orderly fashion within bone marrow of mesenchymal/endothelial/vascularate
What is haemopoiesis regulated by
Genes/transcription factors/microenvironment
Disruption of regulation of haemopoiesis
Proliferation and differentiation is disrupted - lead to leuakemia/bone marrow failure
Haemopoietic growth factors
Hormones which bind to surface receptors and regulate proliferation/differentiation of HSCs
Red cell production
Erythropoiesis is regulated by erythropoietin (made in kidney)
Granulocyte and monocyte production?
Regulated by cytokines like interleukins
Megakaryocytopiesis and platelet production
Thrombopoietin
Lymphoid differentiation
Lymphoid progenitor splits into 3 :
B cell progenitor - humoral (antibody)
T cell progenitor - cellular (cytokine)
NK cell progenitor - cellular (cytokine/natural killer)
Myeloid differentiation
Common myeloid progenitor splits into two
Granulocyte-monocyte
MEP (splits into erythroid and megakaryocytic)
As differentiation progresses?
Self renewal and lineage plasticity decrease
Polychromatic RBCs
RBCs are immature - appear bluish grey
Reticulocytes
Higher RNA content (different methylene blue stain is used for this)
Erythropoiesis
Myeloid progenitor - porerythroblast - erythroblast - erythrocytes
4 components needed for erythropoiesis
Iron
Vitamin B12
Folic Acid
Erythropoietin (regulates everything)
Low iron deficiency
Anaemia - microcytic (small RBC size) ; due to loss of blood (gastro/menstrual)/reduced intake/increased requirement (pregnancy) or inflammation/chronic disease
Hookworm
Helminths - blood loss leading to anaemia
What do microcytic RBCs look like
Hypochromic (smaler/paler)
b12/folic acid deficiency
Anaemia - macrocytic (RBCs have a large size) - leads to megaloblastic anaemia - they grow but cannot divide due to lack of B12/Folic Acid
Hypoxia
Oxygen is not present in sufficient amounts at tissue level to maintain adequate homeostasis
Erythropoietin is glycoprotein synthesised in response to
Hypoxia so there is demand feedback loop - it stimulates bone marrow to produce more RBCs
Iron 2 major functions
Oxygen transport haemoglobin
Mitochondrial proteins (cytochromes a b c for apt production)
Iron deficiency shows
Koilonychia
Glossitis and Angular Stomatitis
Hypochromic and microcytic
Where is iron absorbed
Duodenum
Animal derived iron
Best form - ferrous - FE2+
Iron in food (dariy/eggs etc too)
Ferric - Fe3+ - has to be reduced first by vitamin c for example before absorption
Iron homeostasis
Excess iron is toxic to heart/liver and no way to excrete iron so tightly controlled ; 1-2mg per day is absorbed
How is iron harmful?
Free radicals that can damage body tissues
Fe3+ foods also contain
Phytates which bind to iron and reduce its absorption
Iron forms/transport
Reduced to Fe2+ by duodenal cytochrome b ; either taken up as ferritin or in ferric form (fe3+) and transported to plasma via ferroportin
When iron is needed for erythropoiesis
Bound to transferrin which delivers it to bone marrow
Enterocytes
Columnar epithelial cells in gut lining
Action of hepcidin
Binds to ferroportin and induces its internalisation preveting efflux of iron from enterocyte
iron stores in cell is called
Ferritin
What does hepcidin do to ferritin
When iron stpres are full then upregulation of hepcidin and iron absorption is limited and vice versa for when increased erythropoeisis
Action of hepcidin
ACTS ON FERROPORTIN MEANING FE3+ CANNOT BE SECRETED INTO THE PLASMA FROM ENTEROCYTE
WHEN ERYTHROPOEISIS IS NEEDED THEN DOWNREGULATION OF HEPCIDIN = ALLOWING EFFLUX OF FE3+ INTO PLASMA WHICH CAN GO TO BONE MARROW (TRANSFERIN) AND CREATE RBC STEM CELLS
Iron deficiency
Microcytic
Hypochromia
How many days do rbcs circulate for
120 - then phagocytosed by macrophages in the spleen and haem is recycled - this is what produces bile
Folic acid
Enzyme reaction : dUMP to dTTP (synthesis of thymidine)
Vitamin B12
Cofactor in krebs and cofactor in regenerating tetrahydrofolate WHICH IS ESSENTIAL FOR dUMP to dTTP - so THEY ARE LINKED
Failure of RBCs due to B12/folate deficiency
Megaloblastic anaemia - which is a cause of macrocytic anemia
Folate absorbed mainly in
Duodenum/jejunum ; mainly from leafy greens and demand increases during pregnancy/sickle-cell anaemia where there is increased RBC production
B12
Only found in foods of animal origin - cleaved from food proteins by hcl first and then binds to haptocorrins - then cleaved from this and binds to IF which is essential for absorption in the ileum
In circulation B12 is bound to enzyme
Transcobalamin
Situations of B12 deficiency
Vegan diet
Lack of stomach acid
Autoantibodies - production of IF disrupted - PERNICIOUS ANAEMIA
Diseases in ileum that reduces absorption
Shortened red cell survival
Haemolysis
Disruption of vertical linkages in membrane proteins
Hereditary spherocytosis - round with no central pallour - loss of membrane without loss of cytoplasm so membrane rounds up - removed by spleen
Disruption of horizontal linkages
Hereditary elliptocytosis
Haemolysis due to
Integrity of membrane
Haemoglobin structure/function
Cellular metabolism
G6PD deficiency
Glucose 6 phosphate produces NADPH in PPP ; NADPH provides reducing power for maintaining reduced glutathionine which is a vital antioxidant in RBCs
G6PD maintains reducing power of NADPH that enavles glutathioine protection
Deficiency of G6PD means
Red cells vulnerable to oxidant damage
What does G6PD deficiency look like?
A lot of irregularly contracted cells (bite cells) - smaller and lost central pallour
Polycythaemia
Too many red blood cells in circulation ; Hb/RBC/Hct all increased
Cause 1 of Polycythaemia
Elevated erythropoietin levels
Cause 2 (independent)
Intrinsic bone marrow disorder - myeloproliferative disorder
Polycythaemia leads to
Thick blood - high viscosity which could result in thrombosis - removed via venesection
