Haematology Flashcards
Granulocyte and monocytes growth factors?
G-CSF, GM-CSF, cytokines (interleukins)
Megakaryocytopoiesis and platelet production growth factors?
Thrombopoietin
Iron deficiency symptoms?
Koilonychia, glossitis, angular stomatitis
What are B12 and folate needed for?
dTTP synthesis for synthesis of thymidine for DNA synthesis
Disruption of vertical linkages of RBC?
Disruption of ankyrin/spectrin vertical linkages causes hereditary spherocytosis (spherocytes, autosomal dominant)
Disruption of horizontal linkages on RBCs?
Hereditary elliptocytosis (also in iron deficiency)
What is G6PD important for?
Hexose monophosphate (HMP) shunt, coupled to glutathionine metabolism, protects RBC from oxidative damage.
Bohr effect?
High CO2, low pH, right shift, O2 release.
cooperativity - O2 affinity of Hb increases as oxygen is added to it.
2,3-BPG
Biphosphoglycerate, competitive inhibitor of O2, right shift. Bind to beta-globin chain in central cavity.
Heinz bodies?
In G6PD deficiency, irregularly contracted cells
MCV?
Hct
—— L
RBC
MCH?
Hb
—— g
RBC
MCHC?
Hb
—— g/L
Hct
Myeloid growth factors?
G-CSF - granulocyte colony-stimulating factors
M-CSF - macrophage colony-stimulating factors
GM-CSF - granulocyte-macrophage colony-stimulating factors
Contents of basophil granules?
Histamine, heparin and proteolytic enzymes.
CML cause?
Translocation between chromosome 9 (tyrosine kinase) and 22, uncontrolled tyrosine activity.
Tyrosine kinase inhibitor treatment.
Vasoconstriction in primary Haemostasis?
Nitric oxide and prostacyclin (vasodilators) concentration lower than endothelin (vasoconstrictor)
Platelet adhesion in primary Haemostasis?
Stick to vessel wall directly to collagen through GPIa or to VWF through GPIb receptors.
Causes activation, from disc to rounded shape. Form spicules to encourage platelet interactions.
Platelets release in primary Haemostasis?
ADP (binds to P2Y12 receptor and thromboxane A2, positive feedback).
Fibrinogen, VWF.
Prostaglandin thromboxane A2 and prostacyclin (from endothelial cells) from arachidonic acid using cyclo-oxygenase.
Fibrinogen?
Activates platelets, conformational change, binds to GPIIb/IIIa, platelet plug.
Anti-platelet drugs?
Aspirin - irreversibly binds COX, platelets cannot produce more but endothelial cells can (as have nucleus).
Clopidogrel - irreversibly blocks ADP receptor P2Y12.
Secondary Haemostasis factors?
TF + VIIa = IX -> IXa + X -> Xa = II -> IIa
IIa = V -> Va, VIII -> VIIIa, XI -> XIa + platelets
XIa = IX -> IXa
IXa + VIIIa = X -> Xa + II -> IIa
IIa = fibrinogen -> fibrin.
Vitamin K?
Needed for carboxylation of glutamic acid residues in factors II, VII, IX + X
Anticoagulant drugs?
Heparin - potentiates antithrombin which inactivates Xa and IIa.
Warfarin - vitamin K antagonist, reduces synthesis of factors II, VII, IX + X by liver.
Direct oral anti coagulants - inhibit thrombin or factor Xa.
Protein C?
Thrombin binds to thrombomodulin, activates protein C, which inactivates cofactors Va and VIIIa. In presence of cofactor protein S.
Fibrinolysis?
t-PA (tissue plasminogen activator) + plasminogen bind to lysine residues on fibrin together which converts plasminogen -> plasmin.
Plasmin breaks down fibrin, fibrinogen and factors Va and VIIIa.
Plasmin inhibited by anti plasmin + alpha-2-macroglobulin.
Thrombolytic therapy and antifibrinolytic drugs?
Thrombolytic therapy - recombinant t-PA for ischaemic stroke + pulmonary emboli.
Antifibrinolytic drugs - tranexamic acid - synthetic derivative of lysine that binds to plasminogen and prevents activation through competitive inhibition.
PT vs APTT?
PT - extrinsic factors, prolonged = reduction in activity of VII, X, V, II or fibrinogen. Recombinant thromboplastin used as source of TF and phospholipid.
APTT - intrinsic factors, prolonged can be haemophilia A (factor VIII deficiency), B (factor IX deficiency), factor XI deficiency, or factor XII deficiency (no bleeding).
Proteins in plasma?
Make up 7% of plasma.
Serum albumin (55%) - produced in liver, transports lipids, hormones and ions. Maintains osmotic pressure of plasma.
Globulins (35%) - alpha, beta and gamma globulins.
Alpha globulins?
Alpha-1-antitripsin - inhibits proteases to protect tissues from enzymes like neutrophil elastase.
Alpha-2 - haptoglobulin (binds to haemoglobin then removed from spleen, used in haemolytic anaemia diagnosis) and alpha-2 macroglobulin (protease inhibitor which inactivates fibrinolysis).
Beta and gamma globulins?
Beta globulin - complement protein C3 + C4, transferrin from liver (transports iron and ferritin).
Gamma globulin - immunoglobulins, acute phase C reactive protein.
A, B, and O antigen formation?
specific monosaccharides added onto common glycoprotein and fucose stem
A - enzyme adds N-acetyl galactosamine to H stem.
B - enzyme adds galactose to H stem.
O - only H stem.
RBC cell membrane?
Biconcave, lipid bilayer supported by protein cytoskeleton. Has transmembrane proteins which maintain integrity, elasticity and shape.
Haem group made of?
1 porphyrin ring and Fe2+.
Iron recycled in haemolysis, whilst catabolism releases bilirubin which is excreted in bile.
Foetal vs adult Hb?
Adult - 2 alpha and 2 beta globin chains.
Foetal - 2 alpha and 2 gamma globin chains.
ALL?
Acute lymphoblastic leukaemia - mostly in children.
Bone marrow infiltrated with lymphoblasts so impaired haemopoiesis and circulating lymphocytes
Thrombocytopenia so easy bruising, pale skin due to anaemia.
CLL?
Chronic lymphocytic leukaemia
Smear/smudge cells
AML?
Acute myeloid leukaemia
Auer rods (abnormal lysosomes), myeloblasts, monoblasts.
Anaemia symptoms, spontaneous bleeding, petechiae.
CML?
Philadelphia translocation between chromosome 9 and 22, band forms, left shift. Eosinophils and basophils elevated.
Tyrosine kinase inhibitors needed
What is in FFP and who is it given to?
Clotting factor - given for prolonged APTT + PT.
What is in cryoprecipitate and who is it given to?
Contains fibrinogen, factor VIII, VWF + fibronectin.
Polycythaemia vera?
Too many RBCs, blood doping/over transfusion, increase in erythropoietin, increases Hb, RBC + Hct.
pseudo = decreased plasma volume
Haematocrit?
Percent by volume of RBCs in blood
Iron functions
O2 transport in haemoglobin and mitochondrial proteins
Stored at ferritin in liver, absorbed in duodenum
Transferrin transports iron in plasma
Antithrombin?
Inactivates thrombin and factor Xa, potentiated by heparin.
