Haemopoiesis and Anaemia Flashcards
Where does production of blood cells occur?
RBCs, platelets and most white blood cells in the bone marrow - extensive throughout infant, but more limited distribution in adulthood with predominantly the pelvis, sternum, skull, ribs and vertebrae.
When looking at disorders of bone marrow, how is a sample obtained?
You can do a Trepline biopsy or more specifically look at particles from a bone marrow aspirate (iliac crest of pelvis).
Haemopoiesis is controlled by hormones, how are lymphocytes derived?
Multipotential haematopoietic stem cells (Hemocytoblast) –> common lymphoid progenitor (+ common myeloid progenitor) –> small lymphocytes –> B and T
How are platelets derived?
Multipotential haematopoietic stem cells (Hemocytoblast) –> (common lymphoid progenitor) + common myeloid progenitor –> Megakaryocyte (+ erythrocyte + myebolast) –> thrombocytes.
How are erythrocytes derived?
Multipotential haematopoietic stem cells (Hemocytoblast) –> (common lymphoid progenitor) + common myeloid progenitor –> erythrocyte (+ Megakaryocyte + myebolast).
How are white blood cells other than lymphocytes derived?
Multipotential haematopoietic stem cells (Hemocytoblast) –> (common lymphoid progenitor) + common myeloid progenitor –> (Megakaryocyte + erythrocyte) myebolasts –> monocytes, eosinophils, neutrophils, basophils.
Haemopoiesis is controlled by cytokines, which ones trigger the production/release of which blood cells?
Megakaryocyte - TPO and GM-CSF, Granulocytes - G-CSF and GM-CSF, Lymphocytes - ILs and TNFs play a major role.
Control and removal of blood cells is via the ______________________ system, a network in _______ and tissues, part of the immune system containing ___________ cells: kupffer cells, monocytes, neutrophils, tissue history test and ________ cells in the CNS. Cells of the RES can identify and mount an appropriate response to foreign _________.
Reticuloendothelial Blood Phagocytic Microglial Antigens
What are the major organs and their roles in the Reticuloendothelial system?
The spleen and the liver. All blood cells pass through the spleen and RE cells can dispose of them (particularly damaged/old RBCs). Extracellular fluid travels via the lymph to the lymph nodes.
Measuring peripheral blood counts, you want to know how many, how effective me how large the cells are. Ranges can vary between populations and laboratories, but roughly what do you want?
Hb adult male - 130-180g/L, female - 115-165g/L,
RBC (count) m - 4.5-6.5x10(power of 12) and f - 39-5.6/L,
MCV (mean cell volume) - 80-100fL,
WBC - 4-11 x10(power of 9)/L,
Platelet count - 150-400x10(power of 9)/L.
What are the functions of red cells?
Deliver oxygen to tissues, carry Hb, maintain Hb in reduced (ferrous) state, generate ATP (to maintain membrane) and maintain osmotic equilibrium.
RBCs should last ___ days, are _______ in shape, a flexible disc ___micrometers in diameter, have a lipid bilayer with membrane ________. The shape facilitates passage through the _____________, which had a minimum diameter of ___micrometers. Changes in components of the cell membrane (congenital/__________), will Chang the RBC ________.
120 Biconcave 8 Proteins Microcirculation 3.5 Acquired Shape
Haemoglobin is a tetramer of 2 pairs of _______ _______, each with their own ____ group (containing __) - they may exist in 2 ___________. There are globin gene clusters of chromosomes ___ and ___ expressed at different stages of _____. Globin chains are synthesised independently and then ________.
Globin chains Haem Fe Configurations 10 and 16 Life Combine
When does the switch from foetal to adult haemoglobin occur and why does it matter?
The switch occurs at 3-6 months and the variants have different peptides and therefore properties.
What do haem molecules do?
Haem molecules combine reversibly with oxygen and carbon dioxide to carry the former from the lungs to the tissues and do the opposite for the latter.
What do the globin chains on Hb do?
Protect the haem from oxidation, confer solubility and permits variation in oxygen affinity (and shape).
What is the shape of the oxygen binding curve and what is it influenced by?
Sigmoid, facilitated by the change in shape of Hb - position of curve shifted under certain conditions.
What happens to the haemoglobin components in its catabolism?
The globin chains are split into amino acids that are recycled. The haem goes into Fe reused and bilirubin in a negative feedback loop of RE cells, with excess RBC destruction causing excessive bilirubin formation (should be excreted in bile from gall bladder), leading to jaundice.
How is erythropoiesis specifically controlled?
Reduced pO2 is detected in interstitial peritubular cells in the kidney, so increased production of erythropoietin (hormone), which stimulates the maturation and release of red cells from the bone marrow - Hb rises, pO2 rises, so erythropoietin production falls.
What are the 2 metabolic pathways in red cells?
Glycolysis - glucose –> lactate (ATP generated).
Pentose phosphate pathway - G-6-P metabolised (produces NADPH).
Iron - an essential element in all living cells, transports and ______ oxygen and is an integral part of many ________ (for energy metabolism, neurotransmitter production, collagen formation and immune system function). There is no mechanism of ________ Fe and the quantity of ______ Fe is carefully controlled. __________ is very common and a major cause of global health problems.
Stores Enzymes Excreting Blood Deficiency
What are the different types of available and stored Fe?
Available: Hb (2000mg), myoglobin (oxygen reserve in muscles), tissue Fe (enzyme systems e.g. Cytochromes) and transported/serum Fe (3mg).
Stored: Ferritin (soluble, can do a biochemistry test), Haemosiderin - macrophage Fe (can be stained for, insoluble, 1000mg).
More iron is used during pregnancy, where does most of the active iron come from?
80% of active iron comes from recycling within the body, not gut absorption.
Macrophages consume old, senescent RBCs, there are mainly splenic macrophages and Kupffer cells of the liver, where is most of the stored Fe in the liver?
95% of stored Fe in the liver is as ferritin in hepatocytes. Haemosiderrin makes up the remaining 5% in the Kupffer cells.
1-2mg of Fe enters and leaves the body each day, how?
A small amount of iron is lost each day e.g. Skin and gut cells. In the diet, haem Fe is a better source than non-Haem. 10-15mg per day is needed in the diet and there is Fe supplementation for instance in cereals.
What are the differences in initial absorption of haem and non haem Fe?
When haem enters enterocytes, the iron released is ferrous, but in non haem it mainly exists as ferric. This needs to be reduced before it is transported across the intestinal epithelium. Different proteins are involved in absorbing different types. Stomach acid may reduce ferric iron for absorption on the apical surfaces of the duodenum and upper jejunum.
What happens once Fe is absorbed in the intestine?
It is either stored as ferritin or transported in the bloodstream. Iron is transported out of the cell by ferroportin - fatal enterocytes have receptors for lactoferrin, the primary source of Fe in infants.
What are transferrin receptors and which type of cell has the most?
Fe is taken into cells by the binding of the iron-transferrin complex to the TfR. Erythroid cells have the highest number of transferrin receptors.
