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Blood - Coggle Diagram

- - - - Made by liver
      - platelets bind to it so little reaches teh bone marrow
      - means they receive less signal to make platelets so platelet number is self regulating
    - - made by kidney adn little by liver
      - 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
      - 34kD glycoprotein, 165 amino acids long, acts as a hormone
      - control
        
        its gene contains an oxygen sensor regions
        
        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
- - - - despite there being no blood flow during diastole there is blood flow in capillaries
      - the driving force for this continuous flow is provided by elastic properties of the walls
      - in systole a greater volume of blood flows into arteries from heart than leaves(because of resistance) so teh elastic expadns to store this excess blood so there is pressure energy in stretched walls
      - in diastole the stretched walls recoil which exerts pressure on blood which pushes it downstream
  - - - small radius offers resistance to flow
      - this resistnace maintains flow to end organs
      - converts pulsatile systolic-to-diastolic pressure swings in arteries into non-fluctuating pressure in capillaries
      - if blood pressure was not reduced for capillaries, tehy would be damaged by it
  - - - flwo rate is identical through all levels of circulatoy system and equal to cardiac output but branching of capillaries changes cross sectional aria so resistnace changes so actual velocity also changes
      - velocity varies throughout vascular tree and is inversely proportional to total cross sectional area of all vessels at a given level
      - it is much slower than arterioles adn venules and is because it needs to maximise time available for gas exchange
  - - - only peripheral veins (not central veins)
      - skeletal muscle can contract to push when they relax the valves shut to prevent blood falling
- - - - Megakartocytic cells undergo endomitosis (nuclei undergo multiple mitotic divisions, but not cytoplasmic division)
      - This produces very large cytoplasmic volume from platelets bud
    - - Formation of secretory granules
      - formation of demarcation membrane system which produces a large SA of membrane which is needed for platelet shedding
    - - release of protoplatelet packages
      - large cytoplasmic fragments undergo further fragmentation to form individual platelets
      - ends with phagocytosis of nuclei and remaining cytoplasm
- - - - it is the difference in hydrostatic and colloid osmotic pressures between plasma and interstitial fluid
      - Many pressures like capillary blood pressure, plasma colloid osmotic pressure, interstitial fluid hydrostatic pressure, interstitial fluid colloid osmotic pressure
      - it determines whether contents are pulled or pushed, so at one point htere will be a point of no net movement
- - - - yolk sac is primary site of blood cell formation
      - yolk sac is extra embryonic
      - first trimester yields nucleated rbcs
    - - split into hepatosplenothymic phase and medullolymphatic phase
      - in second trimester, hematopoietic stem cells migrate via liver and spleen to seed these tissues
      - these tissues continues haemopoiesis
      - bone marrow is major site of blood cell production by 20 weeks production and increases in third trimester
  - - - 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
- - - - reduction o blood flow
      - formation of a temporary plug in wall of damaged vessel
      - due to interaction of platelets and blood vessels
    - - Conservation of soluble fibrinogen to insuluble fibrin, strengthens initial haemostatic plug
    - - breakdown of fibrin plug after repair of wound
  - - - following injiry blood vessels constrict under a neurogenic response
      - this restricts blood flow to the area
    - - break in endothelial lining which exposes collagen
      - 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
      - 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)
      - info on powerpoint (slide 26)
    - - endothelium produces vWF and BM
      - 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
      - fibrinin slowly dissolved by plasmin causing clot to dissolve
      - plasminogen converted to plasmin by tissue plasminogen activator
    - - it is an important secondary messenger for activation
      - phospholipid turned into arachidonic acif by phospholipase; then into endoperoxides (PGG2 and PGH2) by cyclo-oxygenase
      - these turn into Thromboxae A2 by thromboxane synthase
      - thromboxane suppresses cAMP synthase which elevates ca2+ levels
  - - - 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
    - - proteins with haemostatic function like fibrinogen, thrombospondin, and plasminogen
      - growth factors like PDGF, TGF alpha and beta
      - microbicidal proteins like thrombocidins and kinocidins
      - PDGF (platelt derived growth factor) acts as mitogen for fibroblasts and chemokine for neutrophils
      - 5-HT (serotonin) and Thromboxane helps vasoconstriction
  - - - Filamin binds actin filament to neighbouring filament
      - gelsolin cuts actin filaments and their ends
      - Profilin and Arp2/3 polymerises actin
    - - gelsolin levels increase this fragments existing filaments
      - cofilin activity increase and filamin decrease, this changes cell/platelet shape
      - this change means platelet becomes rounder and larger
    - - Arp2/3 and profilin increase resulting in filamin assembly
      - this changes platelet shape
- - - - discoid shape
      - loose nucleus and no mitochondria and ER
      - cytoskeleton
        
        the cell forms spectrin tetramers which are linked to a complex of actin, tropomyosin and protein 4.1
        
        both ends of actin are capped to stop growth
        
        Spectrin is a large dimeric protein consisting of spectrin alpha and beta
        
        the numerous cytoskeleton makes the cell very flexible
      - contain haemoglobin, binds oxygen in haem group
      - Old people
        
        rbcs only live for 4 moths
        
        but as people age they become stiffer and lose membrane flexibility
        
        they are fragile and more likely to rupture; they are engulfed by scavenging macrophages spleen-liver-lymph nodes and bone marrow
        
        the ineterndothelial slit is a tiny hole, and only healthy rbcs can move through it but old abnormal cells cannot and are engulfed by macrophage
      - Lifecycle
        
        a senescent is taken up by a phagocyte and broken down into globin, heme and iron
        
        heme is converted to bilirubin
        
        bilirubin is toxic and causes brain damage but cannot be removed from the body
        
        so hepatocytes turn bilirubin and glucoronic acid with of UDP-glucoronyl transferase into bilirubin diglucoronide (conjugated bilirubin)
        
        this is water soluble and is expelled into the intestine
      - Pathology
        
        membrane cytoskeleton defects
        
        Elliptocytosis: AD, EPB41, SPTA1, or SPTB genes
        
        EPB41: encodes 4.1, SPTA1 and SPTB encode a, b –spectrins
        
        Spherocytosis: AD spectrin deficiency
        
        Metabolic defects
        
        Glucose 6phosphate dehydrogenase (G6PD) deficiency
        
        Pyruvate kinase deficiency
        
        they have no mitochondria so cannot fully convert sugars
        
        Haemoglobin defects
        
        a- and b-globin chain defects
        
        Sickle cell
        
        due to mutation in haemoglobin chain beta-2, point mutation at amino acid 6 (glutamic to valine)
        
        this changes negatively charged amino acid to a hydrophobic, changing the shape which means they are taken out by the spleen
        
        beta-Thalassemia`
        
        Unpaired a-chains aggregate and damage the membrane
        
        Extravascular haemolysis
        
        Inadequate haemoglobin and small rbc
        
        develops if no b globin adn excessive a globin
        
        the abnormal shapes are detected by the spleen and removes them, the lack of rbcs can lead to skeletal deformities
    - - they are both phagocytes and granulocytes
      - have a single, multilobed nucleus
      - make up 50-80% of circulating leukocytes and circulate for about 8 hours, form first line of defence
      - contain primary (azurophilic) granules which contain elastase defensins and myeloperoxidases, and smaller secondary granules which contain lysozyme, lactoferin, gelatinase adn other proteases
    - - stained with eosin
      - mainly kill parasites that cannot be digested
      - bind to antibody coated parasites, degranulate and dissolve the cell surface membrane
      - granules contain
        
        eosinophil peroxidase which binds to microorganism and facilitates killing
        
        major basic protein binds and disrupts membrane of parasites and causes basophils to release histamine by Ca2+ dependent mechanism
        
        eosinophil catitonic protein neutralises heparin and causes fragmentation of parasites
        
        eosinophil derived neurotoxin secretes protein with ribonuclease and antiviral activity
    - - involved in acute inflammatory response
      - important in allergy and hypersensitivity (secrete heparin and heparin)
      - 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
      - non-phagocytic that defend against larger parasites
    - - largest leucocyte
      - 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
      - kidney shaped nucleus and contain fine strands of chromatin
    - - can be T, B or natural killer
      - account for 20-40% of total leukocytes
      - small lymphocyte
        
        nucleus is densely stained with round or pointer shape and occupies majority of cellso cytoplasm is thin basophilic rim
        
        represent 97% of circulating lymphocytes
      - Large lymphocyte
        
        have large slightly indented nucleus surrounded by pale cytoplasm, sometimes with primary granules