erythropoesis Flashcards
what is blood
a mixture of extracellular fluid and cells
fluid (plasma) = 92% water, 7% protein, 1% other
Cells = 90% erythrocytes, rest leucocytes and thrombocytes
describe the structure of erythrocytes
have a typical lipid bilayer membrane of globular proteins
- biconcave disc shape (increases surface area by 20-30%
- elastic and deformable in order to permit passage of capillary (diameters of 3-4mi)
compare cat and dog erythrocytes
Dog:
- uniform size
- central pallor (concave, brighter in middle)
Cat:
- smaller erythrocytes
- anisocytosis (variation in size)
- scarce pallor (less concave)
describe the normal appearance hor horse, ruminant and camelid erythrocytes
horse:
- rouleaux formation (clustering of RBCs in standing blood)
ruminanat:
- crenantion (spiky appearance)
- variation in size
camelid:
- elipsoid
mammalian erythrocytes dont have nuclei
describe the appearance of avian and reptile erythrocytes
- nucleated
- larger
- early stage are rounded and may be binucleated
- occasional cells lose their nucleaus and are termed erythroplastids
- elipsoid
describe the cellular structure of erythrocytes
- metabolically active (require energy to maintain electrolyte gradients across the plasma membrane and of hemoglobin molecules)
- no organelles (no mitochondria) energy is derived by anaerobic metabolism of glucose (advantage is they avoid consumption of any oxygen theyre carrying)
- mammalian erythrocytes have no nucleus (division occurs at stem cell level) in order to increase space for hemoglobin and allow biconcave shape
what are the main roles of erythrocytes
- transport O2 from lungs to cells
- transport CO2 from cells to lungs
describe the makeup of hemaglobin
- globin
2 pairs of peptides: 2x alpha and 2x beta (or gamma, delta or epsilon - species dependent) - central haem group containing iron atom that can bind a molecule of O2
represents 95% of erythrocyte protein
describe how haemoglobin exchanhges O2 and CO2
- in regions of high oxygen concentration (lungs): globin releases CO2 and iron binds to O2 (oxyhaemoglobin)
- in areas of low oxygen concentrations: O2 is released and CO2 bound (carbaminohaemaglobin)
- in hypoxic tissues (lack of O2) a carbohydrate (2,3-diphosphoglyceride) is released. that facilitates release of O2 from erythrocytes
- haemoglobin also binds nitric oxide a neurotransmitter that causes dilation of blood vessels –> permitting maximal tissue perfusion for supply of oxygen/removal of waste products
- carbon monoxide has greater affinity for haem than oxygen; carbon monoxyhemoglobin can lead to a “healthy” cherry red colour of mucous membranes
how are blood cells formed
haematopoiesis
- continuous process of replenishment
- formation of blood cellular components (RBCs, WBCs, platelets)
- process occurs in red bone marrow and spleen
- red marrow found at ends of long bones and in flat bones (ribs, pelvis, skull)
describe locations for erythropoeisis
from stem cells (no nucleus in mature RBC’s)
in the embryo: erythropoeisis occurs in the yolk sac, liver (spleen) and shifts to bone marrow in later foetal stage
after puberty: primarily in marrow of membranous bones (ribs, vertebrae, sternum, pelvis)
in adults: in the bone marrow. sinusoidal capillaries with larger intercellular gaps to allow passage of cells carry cells from bone marrow to blood. inactive marrow is replaced by fat (yellow marrow) but can regain activity by extension from active tissue and from circulatinf stem cells
in fish, what is the most important haematopoetic organ
kidney
describe the appearance of a reticulocyte
bigger than erythrocyte and contains granules (remnant of nucleus)
what is required for erythropoeisis to occur
adequate amounts of:
- protein
- iron
- copper
- folic acid
- vitamins (B2, B6, B12)
Iron is toxic in its free form and is useful for microbes. therefore need to have control over where stored. ~70% as haemoglobin, ~30% bound to ferritin in macrophages in liver, spleen and bone marrow and some bound to transferrin in plasma
what is erythropoetin
a hormone that controls rate of erythrocyte production (particularly in early stages of development (early embryonic -neonatal) since so many RBCs need to be produced.
expressed in yolk sacs, liver, kidney and also spleen/bone marrow
in adult life, produced in kidney(renal failure impacts EPO production)
how is erythrocyte production regulated
- reduced transport of O2 (= low kidney oxygen indictes circulatory failure or anemia and hypoxia)
- increase renal secretion of EPO (transported by the blood to bone marrow from kidney)
- increase production of erythrocytes in the bone marrow (EPO binds to receptors on CFU-E (erythroid cell precursors))
- increase circulating erythrocytes (EPO also accelerates release of reticulocytes)
- restoration of the O2 transport
if tissue needs more oxygen, EPO secreted
how are erythrocytes broken down
As they age:
- lose sialic acid residues from their surface exposing galactose moieties that induce their phagocytosis
- become more fragile
- may become swollen due to failure of normal membran function
rate of red cell turnover correlates directly with basal heat production per kg of bodyweight. the higher the metaboic rate, the higher the embryocyte turnover
average erythrocyte lifespans:
- 70 days in cats
- 120 days in dogs
- 145 days in horses
- 160 days in cattle
lifespan in transfused blood is much shorter (in dogs approx 21 days)
how is iron metabolised after RBC breakdown
- free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species
- iron molecules released from haeme either get conveyed to bone marrow by transferrin or stored as insoluble iron in macrophages and hepatocytes as ferritin
how is iron transported between cells by transferrin
- serum protein in iron transport (synthesized in liver)
- transferrin-iron complexes bind to cell-surface receptors
- internalisation of transferrin-iron-receptor complex
- low cellular pH within endosomes leads to dissociation of iron from transferrin-receptor-complex
- the tranferrin-receptor-complex dissociates at the cell surface recyclin the system for later use
triangle = iron, blue = transferrin, green = transferrin receptor
how is iron stored intracellularly
ferritin
- the primary intracellular iron-storage protein keeping iron in a soluble and non-toxic form
- releases iron in a controlled fashion. it is a buffer against iron deficiency and iron overload (allows easy accessibility when needed and keeps at good level)
haemosiderin
- intracellular complex of ferritin, denatured ferritin and other material (no longer soluble)
- iron within deposits of hemosiderin is very poorly availible to supply iron when needed
- large deposoits may lead to organ damage
explain cases of abnormal RBC breakdown
- mycoplasma haemofelis (bacteria infects RBC and lyses cells)
- neonatal erythrolysis (foals, usually second foal bc ecause mother develops antibodies to foal and transfers to foal via colostrum) (blood group incompatability w/ mother) (maternal antibodies taken up through colostrum lyse RBCs)
iron is transferred from the liver to the bone marrow as
transferrin
how is energy derived in the erythrocyte
anaerobic metabolism of glucose
- this allows them to avoif the consumption of the oxygen they carry
