anat.17

• 1) Formed elements- cells and platelets
• 2) ECM- plasma (liquid when not clotted) 
• Blood is 55% plasma, ~45% RBC, and ~1% buffy coat=platelets+WBC

• 90% water
• 1% dissolved ions and gases
• 9% plasma proteins

• Albumin
• Globulins- alpha, beta, and gamma 
• Clotting proteins - fibrinogen, prothrombin etc
• Complement proteins
• Plasma lipoproteins - LDL etc

Plasma with clotting factors removed

• Modified H&E stain
• Blue=acid, pink=protein, purple=glycoprotein 

99%

Biconcave shape increases surface area of plasma membrane to facilitate gas exchange

• RBC deficiency
• can either be metabolic or genetic

• Few cytoplasmic organelles
• Develop with a nucleus, but no nucleus in fully differentiated cells
• Cytoplasm is packed with hemoglobin which binds O2 and CO2
• Sub-plasmamembranous cytoskeleton maintains RBC shape and flexibility and is important for movement through capillary beds

Carbonic anhydrase catalyzes the reaction of CO2 and H2O to hydrogen carbonate.  Hydrogen carbonate is part of the bicarbonate buffer system.  Bicarbonate ion is actively transported out of RBCs.

• ~120 days
• Loss of cytoskeleton integrity with increasing RBC age leads to a slowing in small blood vessels and fragility; this targets the aged RBCs for destruction

• 1)  glycophorins- membrane anchors for cytoplasmic adaptor/linker complexes
• 2)  Band 3 - membrane anchor and anion transporter
• 3)  Ankyrin & Band 4 - adaptor/linkers to the RBC cytoskeleton

Granulocytes and agranulocytes

• Important for innate immunity
• cytoplasm of granulocytes contain characteristic cytoplasmic granules- cell type specific = secretory vesicles

• Most abundant WBC's (60-70% of all WBC's)
• Multilobed nucleus (polymorphonuclear cells - PMNs)
• Granules contain anti-bacterial enzymes- secretory vesicles and pale/neutral in colour
• Very short-lived (days)
• 1st responders during innate immune response

• Long-lived (1-2 years)
• Initiate/amplify innate immune response
• Large granules are highly basophilic with histamine and heparin- stain darkly and obscure nucleus
• Also contain chemoattractants that they release to attract other granulocytes to amplify response

• ~2% of WBC's
• characteristic pink eosinophilic dense-cored/"cat's eye" granules
• Short-lived (1-2 weeks in Conn tissue)
• Active in late stages of innate and adaptive immune response

• 1)  Neutrophils
• 2)  Basophils
• 3)  Eosinophils

• Few cell-type specific granules by light microscopy
• Do have some non-specific granules = lysosomes

• 1)  Monocytes
• 2)  Lymphocytes

• Largest circulating blood cell
• ~5% of circulating WBC
• Differentiate into macrophages in connective tissue (phagocytic, antigen-presenting cells)

The movement or passage of blood cells, especially white blood cells, through intact capillary walls into surrounding body tissue

• ~25% of WBCs
• Round nucleus, pale rim of cytoplasm in unactivated lymphocytes
• Involved in adaptive immunity
• B-lymphocytes - humoral/secreted antibody-mediated adaptive immunity
• T-lymphocytes - cell-mediated adaptive immunity

• Membrane-bound cell fragments (no nucleus)
• Contain granules/secretory vesicles
• Contain integrins and cytoskeletal elements
• Normally free floating in circulating blood

• Critical for blood clotting - hemostasis
• Platelet integrins/focal adhesions bind sub-endothelial collagen in wounded blood vessels

Collagen binding and paracrine signals from endothelium

• Thrombospondin - increases platelet-platelet adhesion
• Platelet factor 3 - facilitates clotting cascade to generate fibrin fibers from soluble fibrinogen

• Megakaryotes in the bone marrow - hematopoetic cords
• Demarcation channels fuse to release clusters of protoplatelets which fragment further to form platelets which are released into venous spaces of bone marrow to enter blood stream

Platelet malfunctions/inability to activate; come from loss of function mutations in platelet integrins

A lack of clotting

• Identify chronic infection due to mature WBC increase in peripheral blood
• Alternately, identify leukemia due to immature blast increase in peripheral blood

• Huge numbers of immature WBCs (granulocytes/myeloblasts)
• Initiated by chromosomal 9:22 translocation
• Rise to 'activated' BCR-Abl kinase (receptor-associated)
• Causes hyperstimulation of proliferation in myeloblasts
• Gleevac (STI-512) is an Abl inhibitor