Haematology

• Composition and function of blood

  • Adult = 5L
  • Makes up 7% of body weight
  • Fluid connective tissue
  • Plasma: 55% of blood, 92% water, 7% proteins, 1% other solutes (electrolytes, nutrients, respiratory gases and waste)
  • Function = transport inorganic/organic molecules, formed elementsand heat
  • Erythrocytes = 4.2-62 million/mm2
  • Buffy coat = platelets, leukocytes, neutrophils, lymphocytes, monocytes, eosinophiles, basophils
• Haematopoiesis

  • Hemocytoblast = can turn into any blood cells depending on what it is acted upon by (growth factor or cytochymes)
  • Myeloblast = found in bone marrow Erythropoiesis
• Erythropoiesis

  • Reticulocyte: blue when stained
  • As you eject the nucleus, haemoglobin is produced. Ejected at normoblaststage.
  • Erythropoiesis growth factor = erythropoietin (EPO) (produced in the liver)which acts on precursor cells in bone marrow to commit cell to erythrocyte
  • Other requirements = Fe, V.B12, B9 (folic acid), intrinsic factors and aminoacids
• Occurance of erythropoiesis

  • Foetus: early in yolk sac → liver and spleen → later in bone marrow
  • Infant: all in bone marrow
  • Adult: only red bone marrow (ribs, vertebrae, skull, upper end of long bones)
  • Rate = 2-3 million RBCs/second
• Erythrocyte structure and function

  • Biconcave disk shape
  • Flexible
  • Readily deformed
  • Lifespan =120 days
  • Contents = haemoglobin
  • Function = circulate O2, remove CO2
• Causes of hypoxia

  • Increase in exercise
  • High altitude
  • Smoking
  • Bleeding
• Haemoglobin (Hb)

  • 280 million/RBC
  • Synthesis begins at proerythroblast
  • 65% at erythroblast stage
  • 35% at reticulocyte stage
  • Transports O2 from lungs to tissues
  • Transports CO2 from tissues to lung
  • Females have less Hb than males
  • 4 subunits each bound to a Haem group
  • In the Haem group is a ferrous ion (Fe2+)
  • Fe2+ can reversibly bind to 1 oxygenmolecule
• Anaemia

  • Definition = haemoglobin concentration in whole blood is below the acceptednormal range
  • Men = 13.5 g/dL <
  • Females = 12g/dL <
  • Causes decrease in RBC production, increase in RBC destruction and bloodloss
• Iron deficiency anaemia

  • Most common anaemia
  • Hypochromic = paler RBCs
  • Microcytic RBS
  • Decreased mean cell volume
  • Causes = pregnancy, bleeding from GI tract (ulcer, malignancy),malabsorption, menorrhagia, malnutrition
• Megaloblastic anaemia

  • Vitamin B12 or folate deficiency
  • Abnormal Hb concentration
  • Macrocytic
  • Increased mean cell volume
  • Causes = pregnancy, elderly and dietary deficiency
• B12 deficiency

  • need of intrinsic factor secreted by the stomach for its absorption
  • Causes of lack of IF are precarious anaemia and Crohn’s and coeliac disease
  • Treatment includes B12 muscular injections
• Sickle cell anaemia

  • Hereditary, African, W.Indian
  • Abnormal Hb structure
  • Sickle cell, RBCs stuck in blood vessels
  • No cure
• Thalassaemias

  • Hereditary: mediterranean, Middle/far East
  • Abnormal Hb production (alpha and beta thalassaemia)
• Platelets

  • No nucleus
  • 2-3 um
  • Contain granules
  • Megakaryocyte cytoplasm (break of cytoplasm to form 1400 platelets)
  • Production controlled by number of circulating platelets (-ve feedback)
  • Growth factor: thrombopoietin (TPO)
  • Lifespan: 7-10 days
  • Described as a fragment cell (very small)
• Extrinsic pathway● Initiated by tissue factor,

  present in endothelial lining of blood vessels

  ● Factor III binds to factor VII to form: tissue factor FVIIa complex

  ● FVIIa complex binds to factor C (FX) to activate and form FXa
• Intrinsic pathway● More efficient than extrinsic
• Common pathway

  • Prothrombinase consists of FXa and FVa as a co-factor
  • Activates prothrombin to form thrombin
  • Thrombin converts fibrinogen to fibrin
• Requirements for coagulation (extrinsic and intrinsic pathway)

  • Ca (speeds up reactions) + vitamin K (production of certain clotting factors inthe liver (prothrombin))
  • Any disorder that decreases Ca2+ concentration will impair blood clotting
• Control of clotting* Anticoagulants

  • Antithrombin: inhibits thrombin (and other other factors
  • Heparin: released by basophils and mast cells, cofactor that acceleratesactions of antithrombin
• Fibrinolysis

  • Where fibrin clot is broken down
  • Enzyme: plasmin
  • Produces fibrin degradation productions
• ABO blood groups

  • Surface antigens + opposing antibodies = agglutination and hemolysis
  • AB = codominant

  Rh (D) blood group

  • Rh +ve/-ve depending on presence of D antigen (-ve = no protein)
  • Rh (-) individual will not usually contain anti-Rh (D) antibodies
  • Requires sensitisation by exposure to Rh+ RBCs
• Haemolytic disease of the newborn

  • Breakdown of placental tissue can lead to mixing of blood during birth
  • Baby (Rh+) blood goes into mother (Rh-) → response against foreign blood,mother produces anti D/Rh antibodies → attach to baby’s RBC → haemolysis
  • 72 hours to mount an immune response
  • Antibodies stay in system, can be fatal to 2nd pregnancy
  • anti-D drugs prevent anymore antibody production
  • Macrophages break down blood in the liver and spleen
• Leukocytes

  • Neutrophils: 60-70%
  • Lymphocytes: 20-25%
  • Monocytes: 3-8%
  • Eosinophils: 2-4%
  • Basophils: 0.5-1% (Never Let Monkeys Eat Bananas)
  • All produced from multipotential hematopoietic stem cell
  • Only the common lymphoid progenitor produces lymphocytes (B, T andplasma cells)
  • Nucleated
• Characteristics of leukocytes

  • Can migrate out of the blood stream - process: extravasation (diapedesis)through endothelium
  • Capable of amoeboid movement (projections from the cytoplasm,pseudopodia, allows movement)
  • Attracted to specific chemical stimuli
  • Neutrophils, eosinophils and monocytes are capable of phagocytosis
  • Normal count: 4-10 x9/L in blood
  • Granulocytes = -phil
  • Agranulocytes = -cytes
• Granulocytes include: Neutrophils, Eosinophils and Basophil
• Neutrophils

  • Largest majority
  • 9-15 um, bigger that erythrocytes
  • 1st line defence against bacterial infection
  • Phagocytic
  • Mobile
  • Circulate blood for 10 hours
  • Major constituent of pus
• Eosinophils

  • Second largest majority
  • 10-12 um
  • Bilobar nucleus
  • Circulate blood for 8-12 hours then migrate to tissues
  • Survive 1-3 days
  • Release toxic compounds
  • Allergies and asthma
  • Combat parasitic infections
  • Attack bacteria, protozoa and debris
  • Eosinophilia = increased number
• Basophil

  • Smallest majority
  • Bilobar nucleus
  • Large cytoplasmic granules
  • Inflammatory response
  • Granules of histamine and heparin
  • Unknown lifespan
  • Precursor to mast cells? Share common bone marrow precursor
• Monocytes

  • 20um - largest
  • Kidney shaped nucleus
  • Extensive cytoplasm
  • Little function in blood
  • Phagocytic
  • Migrate out of circulation after 3-4 days
• Lymphocytes

  • Smallest
  • 6-15 um
  • Lives weeks to several years
  • Central role in all immunological defence mechanisms
  • Circulate lymphoid tissues and other tissues via blood and lymphaticvessels
  • Types include:
  • T cells - mediate cell mediated immunity (transplant rejection)
  • B Cells - differ into plasma cells, secrete antibodies (humoralimmunity)
  • Natural killer cells - immune surveillance, prevent cancer
  • All increase with viral or bacterial infection