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What does blood consist of?
- 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
Describe the components of plasma
- 90% water
- 1% dissolved ions and gases
- 9% plasma proteins
Provide examples of plasma proteins.
- Globulins- alpha, beta, and gamma
- Clotting proteins - fibrinogen, prothrombin etc
- Complement proteins
- Plasma lipoproteins - LDL etc
What is serum?
Plasma with clotting factors removed
What is Wright's stain?
- Modified H&E stain
- Blue=acid, pink=protein, purple=glycoprotein
RBCs make up what percentage of total circulating blood cells?
What's the functional relevance of the biconcave shape of RBCs?
Biconcave shape increases surface area of plasma membrane to facilitate gas exchange
What is anemia?
- RBC deficiency
- can either be metabolic or genetic
Describe the structure of RBCs.
- 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
The cytoplasm of RBCs contains carbonic anhydrase. What is the significance of this?
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.
What is the lifespan of a RBC?
- ~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
Name three types of cytoskeletal proteins in RBCs.
- 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
What are the two general types of WBCs?
Granulocytes and agranulocytes
- Important for innate immunity
- cytoplasm of granulocytes contain characteristic cytoplasmic granules- cell type specific = secretory vesicles
What are neutrophils?
- 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
What are basophils?
- 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
What are eosinophils?
- ~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
Name the three types of granulocytes.
- 1) Neutrophils
- 2) Basophils
- 3) Eosinophils
List two characteristics of agranulocytes.
- Few cell-type specific granules by light microscopy
- Do have some non-specific granules = lysosomes
What are the two types of agranuloctyes?
- 1) Monocytes
- 2) Lymphocytes
What are monocytes?
- Largest circulating blood cell
- ~5% of circulating WBC
- Differentiate into macrophages in connective tissue (phagocytic, antigen-presenting cells)
What is diapedesis?
The movement or passage of blood cells, especially white blood cells, through intact capillary walls into surrounding body tissue
What are lymphocytes?
- ~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
What are platelets?
- Membrane-bound cell fragments (no nucleus)
- Contain granules/secretory vesicles
- Contain integrins and cytoskeletal elements
- Normally free floating in circulating blood
What is the functional role of platelets?
- Critical for blood clotting - hemostasis
- Platelet integrins/focal adhesions bind sub-endothelial collagen in wounded blood vessels
What activates platelets?
Collagen binding and paracrine signals from endothelium
What molecules are exocytosed from activated platelets?
- Thrombospondin - increases platelet-platelet adhesion
- Platelet factor 3 - facilitates clotting cascade to generate fibrin fibers from soluble fibrinogen
What produces platelets?
- 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
What is a thrombasthenia?
Platelet malfunctions/inability to activate; come from loss of function mutations in platelet integrins
What is a coagulopathy?
A lack of clotting
What is a differential white count?
- Identify chronic infection due to mature WBC increase in peripheral blood
- Alternately, identify leukemia due to immature blast increase in peripheral blood
Describe the Chronic Myelogenous Leukemia (CML) smear and analysis.
- 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