split into hepatosplenothymic phase and medullolymphatic phase

in second trimester, hematopoietic stem cells migrate via liver and spleen to seed these tissues

bone marrow is major site of blood cell production by 20 weeks production and increases in third trimester

red bone marrow contains stem cells involved in haematopoiesis

red marrow only found in torso and skull, the rest is yellow bone marrow

yellow bone marrow can turn into red when there is continuous increased haemopoietic demand

the spleen and and liver are also capable of producing blood cells and are the main sites of extramedulllary haemopoiesis

haematopoietic stem cells occupy a well protected niche, since bone marrow is a high calorie source

bone provides shelter from harmful irradiation , protection from UV light is an evolutionarily conserved feature of haematopoietic niche

studies have shown that most fish kidney cells that make stem cells have a layer above them of melanocytes for protection

they can self-renew, differentiate into range of lineages and perform slow replication

totipotent can differentiate into all cells, pluri can differentiate into the 3 germ layers (but not extra embryonic tissues), and multi can differentiate to all cell types in one particular lineage

they can divide into 2 daughter cells (symmetric cell division) and also divide wherre one remains a stem cells and other differentiates

they have no nucleus, th ebenefit of no nucleues is more likely to fit through narrow spaces which could otherwise damage it rather than pack more in and the methylene blue stains a network of strands in cytoplasm (RNA)

orthochromatic erythoblast shrink and the nucleus goes to the cell membraen and is then ejected and taken up by the macrophage

these are clusters of cells if the differentiation sequence with a macrophage centre

macrophages also deliver iron for the cells for haemoglobin production

means they receive less signal to make platelets so platelet number is self regulating

released in response to decrease in oxygen, interleukin proteins and CSF-E maturation is stimulated by B12 and folic acid; haemoglobin production by Fe, Cu, Zn, Co, vitamin C

binds hypoxia-inducible factor 2, so it detects this factor which regulates breakdown of hypoxia inducible factor and can result in congenital polycythaemia

EPO binds to dimerised erythropoietin receptor and induces binding of cytosolic STAT5 protein to JAK2 (STAT5 becomes phosphorylated and homodimerises)

phosphorylated STAT5 homodimer translocates into nucleus and after binding to DNA it activates transcription of genes for erythropoiesis

important in allergy and hypersensitivity (secrete heparin and heparin)

new monocytes circulate in blood for a few hours before migrating to tissue and turning into macrophages

the macrophages derived monocytes are more efficient phagocytic cells than neutrophils

thye contain large cytoplasmic granules with suffated or carboxylated acidic proteins like heparin

they are similar to mast cells in connective tissues since they express IgE receptors but differ in expression of c-kit receptors and CD49b

basophilia is an increase in basophils and causes acute hypersensitivity reactions, viral infections and chronic inflammatory conditions

kidney shaped nucleus and contain fine strands of chromatin

nucleus is densely stained with round or pointer shape and occupies majority of cellso cytoplasm is thin basophilic rim

have large slightly indented nucleus surrounded by pale cytoplasm, sometimes with primary granules

melanocytes protect haemopoietic stem and progenitor cells in zebrafish larvae from DNA damage by UV

melanocytes form an umbrella overs HSPCs and protects them

the protection was also found in other fish and the mechanism is evolutionary conserved

Conservation of soluble fibrinogen to insuluble fibrin, strengthens initial haemostatic plug

small membrane bound packets of granular cytoplasm (clotting proteins and cytokines) with no nucleus

Circulating platelets are 1-4um in diameter and 0.5-1 um thick discoids

they contain mitochondria adn SER and are produced by pinching off and shredding of megakarocytes (polyploidy cells)

Megakaryocytes are derived from a multipotent progenitor in bone marrow which becomes lineage restricted to megakarocyte production

inactive platelet is smooth and discoid shape but an active platelet is spiny and sphaeric

proteins with haemostatic function like fibrinogen, thrombospondin, and plasminogen

the granulomere is the central portion of platelet (containing granules and lysosomes) and hyalomere is the peripheral microtubules and microfilaments

cofilin activity increase and filamin decrease, this changes cell/platelet shape

They have an invaginate membrane system, and many receptors like GP2b-CP3a, GP1b and alpha2beta1 integrin

glycocalyx surface coat that contains glycoproteins that help adhesion adn aggregation

coagulation factor receptors, like coagulation factor I is fibrinogen and V, VIII, X, XI, XII, XIII enhance coagulation

PDGF (platelt derived growth factor) acts as mitogen for fibroblasts and chemokine for neutrophils

following injiry blood vessels constrict under a neurogenic response

platelts adhere to collagen, but adhesion requires vWf and factor VIII which act as a bridge between platelet and membrane

there is a release of platelets factors after contraction which further exposes basal membrane and collagen

adhesion triggers change from discoid to irregular shape to adhere to other platelets

receptors for ADP, collagen and thrombin increase on membrane; ADP and thromboxane A2 acts as platelet chemoattractants

platelet activation causes release of vasoconstrictors like A2 adn 5-HT

also releases PGI2 (prostacyclin) to inhibit platelt aggregation and causes vasodilation

binding and extravasation of immune cells and synthesises tissue factor

nitric oxide inhibits platelt activation and promotes vasodilation by raising cGMP levels

phospholipid turned into arachidonic acif by phospholipase; then into endoperoxides (PGG2 and PGH2) by cyclo-oxygenase

thromboxane suppresses cAMP synthase which elevates ca2+ levels

endothelial cells release tissue factor which binds factor VIIa, which converts factor X into Xa, andVon Willebrand factor binds to Gp1B platelet receptor which helps collagen attachment

fibrinogen in plasma binds to activated integrin receptors to bridge platelets, and thrombin acts on fibrinogen to cleave fibrinopeptides adn form fibrin monomer which aggregates to form the clot (Factor XIII crosslinks monomers)

plasminogen converted to plasmin by tissue plasminogen activator