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126 Cards in this Set
- Front
- Back
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What is the function of erythrocytes? |
Carries O2 to tissues and CO2 to lungs
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What is the structure of an erythrocyte?
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- Anucleate and biconcave
- Large surface area-to-volume ratio for rapid gas exchange |
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How long does an erythrocyte last?
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120 days
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What is the source of energy for erythrocytes?
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Glucose:
- 90% used in glycolysis - 10% used in HMP shunt |
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How does an erythrocyte eliminate CO2?
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- Membrane contains Chloride-HCO3- antiporter
- Allows RBCs to export HCO3- and transport CO2 from the periphery to the lungs for elimination |
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What can erythrocytosis lead to?
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Polycythemia / ↑ Hematocrit
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What term is used for varying sizes of erythrocytes?
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Anisocytosis
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What term is used for varying shapes of erythrocytes?
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Poikilocytosis
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What is Anisocytosis mean?
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Varying sizes of RBCs
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What is Poikilocytosis mean?
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Varying shapes of RBCs
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What is an immature RBC called? What does its presence indicate?
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Reticulocyte - immature RBC is a marker of erythroid proliferation
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What structure is involved in primary hemostasis?
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Platelet (Thrombocyte)
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How are platelets made?
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Small cytoplasmic fragments derived from megakaryocytes
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What is the life span of a platelet?
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8-10 days
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What is the function of a platelet?
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When activated by endothelial injury, aggregates with other platelets and interacts with fibrinogen to form a platelet plug
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What are the contents of platelets?
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- Dense granules: ADP and calcium
- α granules: vWF and fibrinogen |
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What is found in the dense granules of platelets?
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ADP and Ca2+
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What is found in the α granules of platelets?
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vWF and fibrinogen
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Where is a large portion of the platelet pool stored? How much?
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1/3 of platelet pool is stored in the spleen
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What causes petechiae?
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Thrombocytopenia or decreased platelet function
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What is the receptor for von Willebrand Factor?
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GpIb
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What is the receptor for fibrinogen?
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GpIIb / IIIa
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What are the types of leukocytes?
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Granulocytes:
- Neutrophils - Eosinophils - Basophils Mononuclear cells: - Monocytes - Lymphocytes |
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What is the function of leukocytes? How many are there normally?
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- Responsible for defense against infections
- Normally 4000 - 10,000 cells / mm3 |
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What is the differential of WBC from highest to lowest?
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"Neutrophils Like Making Everything Better"
- Neutrophils (54-62%) - Lymphocytes (25-33%) - Monocytes (3-7%) - Eosinophils (1-3%) - Basophils (0-0.75%) |
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What is the acute inflammatory response cell?
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Neutrophil
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What are there increased neutrophils?
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Bacterial infections
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What is the function and appearance of Neutrophils?
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- Multi-lobed nucleus
- Phagocytic cell that acts in the acute inflammatory response, especially for bacterial infections |
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What are the contents of neutrophils?
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- Specific granules (smaller and more numerous): ALP, collagenase, lysozyme, and lactoferrin
- Azurophilic granules (larger and less numerous) / lysosomes: proteinases, acid phosphatase, myeloperoxidase, and β-glucuronidase |
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What are the contents of specific granules in neutrophils? How common are they relatively? Size?
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- Contains: ALP, collagenase, lysozyme, and lactoferrin
- More numerous - Smaller |
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What are the contents of azurophilic granules in neutrophils? How common are they relatively? Size? |
Aka Lysosomes
- Contain: proteinases, acid phosphatase, myeloperoxidase, and β-glucuronidase - Less numerous - Larger |
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Under what circumstances might you see hypersegmented neutrophils (5 or more lobes)?
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Vitamin B12 or Folate deficiency
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Under what circumstances might you see increased band cells? What do these represent?
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- Band cells are immature neutrophils
- Reflects states of increased myeloid proliferation (bacterial infections and CML) |
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What is the function and appearance of monocytes?
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- Differentiates into macrophages in the tissues
- Large, kidney shaped nucleus with extensive "frosted glass" cytoplasm |
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What is the function of macrophages?
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- Phagocytose bacteria, cellular debris, and senescent RBCs
- Scavenges damaged cells and tissues - Can function as an antigen-presenting cell via MHC II |
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What is the source of macrophages?
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Differentiates from circulating blood monocytes, activated by γ-interferon
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What is the function of IFN-γ?
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Activates monocytes to macrophages
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What is a cell surface marker for macrophages?
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CD14
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What cells are an important component of granuloma formation (eg, TB and sarcoidosis)?
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Macrophage
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What are the functions of Eosinophils?
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- Defends against helminthic infections via major basic protein
- Highly phagocytic for antigen-antibody complexes - Produces histaminase and arylsulfatase (limits reaction following mast cell degranulation) |
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What is the appearance of eosinophils?
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- Bilobate nucleus
- Packed with large eosinophilic granules of uniform size |
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What can cause eosinophilia?
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- Neoplasia
- Asthma - Allergies - Connective tissue diseases - Parasites (invasive) |
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What do eosinophils produce?
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- Major basic protein (defends against helminthic infections) |
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What type of cell mediates allergic reactions?
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Basophilis
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What are the contents of basophils?
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Dense basophilic granules:
- Heparin (anticoagulant) - Histamine (vasodilator) - Leukotrienes |
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What does an isolated basophilia suggest?
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Uncommon, but can be seen in myeloproliferative disease, particularly CML
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What are the functions of mast cells?
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- Mediates allergic reaction in local tissues
- Can bind to the Fc portion of IgE to membrane - Type I hypersensitivity reactions |
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What do mast cells look like?
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Mast cells resemble basophils structurally and functionally
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What is the effect of mast cells on IgE?
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- Mast cells can bind the Fc portion of IgE to membrane
- IgE cross-links upon antigen binding, causing degranulation, which releases histamine, heparin, and eosinophil chemotactic factors |
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What drug can prevent mast cell degranulation? Function?
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Cromolyn sodium - used for asthma prophylaxis
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What is the function of dendritic cells?
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Highly phagocytic APCs
- Functions as link between innate and adaptive immune system - Expresses MHC class II and Fc receptor on surface |
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What do dendritic cells express on their surface?
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- MHC Class II
- Fc receptor |
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What are Langerhans cells?
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Dendritic cells in the skin
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What are the types of lymphocytes?
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- B cells
- T cells - NK cells |
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What lymphocytes are involved in the adaptive immunity?
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B cells and T cells
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What lymphocytes are involved in the innate immunity?
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NK cells
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What is the appearance of lymphocytes?
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- Round, densely staining nucleus
- Small amount of pale cytoplasm |
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Which cells is part of the humoral immune response? Source? Where does it mature?
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B lymphocytes
- Arises from stem cells in the bone marrow - Matures in the bone marrow |
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What happens to B cells after they have matured in the bone marrow?
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Migrates to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue)
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What happens when a B lymphocyte encounters an antigen?
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- B cells differentiate into plasma cells that produce antibodies and memory cells
- Can function as an APC via MHC II |
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What are the cell surface markers of B lymphocytes?
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CD19 and CD20
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Which cells is part of the cellular immune response? Source? Where does it mature?
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T lymphocytes
- Originates from stem cells in the bone marrow - Matures in the thymus |
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What happens to T cells after they have matured in the thymus?
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T cells differentiate into:
- Cytotoxic T cells (express CD8, recognize MHC I) - Helper T cells (express CD4, recognize MHC II) - Regulatory T cells |
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What is necessary for T cell activation?
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CD28 (costimulatory molecule)
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What are the majority of circulating lymphocytes?
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T cells (80%)
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What does CD mean?
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Cluster of Differentiation
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What are the cell surface markers of T lymphocytes?
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- Helper cells (Th): CD3 and CD4
- Cytotoxic cells (Tc): CD3 and CD8 |
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What is the primary target of HIV?
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CD4+ Helper T cells
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What is the function of plasma cells?
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Produce large amounts of antibody specific to a particular antigen
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What is the appearance of plasma cells?
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- Eccentric nucleus
- Clock-face chromatin distribution - Abundant RER - Well-developed Golgi apparatus |
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What is the cancer of plasma cells?
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Multiple Myeloma
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What are the blood group types?
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- A
- B - AB - O - Rh |
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What kind of antigen and antibodies do patients with blood type A have?
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- A antigen on RBC surface
- Anti-B antibody in plasma |
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What kind of antigen and antibodies do patients with blood type B have?
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- B antigen on RBC surface
- Anti-A antibody in plasma |
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What kind of antigen and antibodies do patients with blood type AB have?
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- A and B antigens on RBC surface
- No antibodies in plasma - Universal recipient of RBCs and universal donor of plasma |
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What kind of antigen and antibodies do patients with blood type O have?
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- Neither A nor B antigen on RBC surface
- Both A and B antibodies in plasma - Universal donor of RBCs and universal recipient of plasma |
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What blood type if the universal recipient of RBCs?
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AB
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What blood type if the universal donor of RBCs?
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O
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What blood type if the universal recipient of plasma?
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O
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What blood type if the universal donor of plasma?
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AB
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What are the potential implications of an incompatible blood transfusion?
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- Immunologic response
- Hemolysis - Renal failure - Shock - Death |
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What type of antibodies are the blood group antibodies? Implications for crossing the placenta?
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- Anti-A and anti-B are IgM antibodies (do not cross placenta)
- Anti-Rh are IgG antibodies (cross placenta) |
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What is the significance of an Rh- mother exposed to fetal Rh+ blood? When?
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- Often exposure occurs during delivery, mother may make anti-Rh IgG
- If there is a subsequent pregnancy, the anti-Rh IgG can cross the placenta and cause hemolytic disease of the newborn in the next fetus that is Rh+ |
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What causes erythroblastosis fetalis?
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- If an Rh- mother is exposed to an Rh+ newborn, often occurs during delivery, mother may make anti-Rh IgG
- If there is a subsequent pregnancy, the anti-Rh IgG can cross the placenta and cause hemolytic disease of the newborn in the next fetus that is Rh+ |
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How do you treat an Rh- mother?
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Rho(D) immune globulin for mother during every pregnancy to prevent initial sensitization of Rh- mother to Rh antigen
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What factors are involved in the extrinsic coagulation cascade pathway?
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- Factor VII activated by Thromboplastin / Tissue Factor to Factor VIIa
- Factor X activated by Factor VIIa to Factor Xa - Factor II (Pro-thrombin) activated by Factor Xa and Va to Factor IIa (Thrombin) - Fibrinogen activated by Thrombin to Fibrin monomers |
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What factors are involved in the intrinsic coagulation cascade pathway?
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- Factor XII activated by collagen, basement membrane, and activated platelets to XIIa
- Factor XI activated by XIIa to XIa - Factor IX activated by XIa to IXa - Factor X activated by IXa and VIIIa to Xa - Factor II (Prothrombin) activated by Xa and Va to IIa (Thrombin) - Fibrinogen activated by Thrombin to Fibrin monomers |
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What is the effect of Bradykinin?
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- ↑ Vasodilation
- ↑ Permeability - ↑ Pain |
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What molecule causes the fibrin / platelet plug to break down to fibrin degradation products?
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Plasmin
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What is Hemophilia A?
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Deficiency of Factor VIII
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What is Hemophilia B?
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Deficiency of Factor IX
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What forms the fibrin clot?
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- Fibrin monomers aggregate with Ca2+ and Factor XIIIa to form a fibrin meshwork
- Fibrin mesh acts to stabilize platelet plug |
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What enzyme converts oxidized vitamin K to reduced vitamin K?
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Epoxide Reductase
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What is the function of reduced vitamin K?
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Acts as a cofactor to activate the coagulation cascade precursors: II, VII, IX, X, and Protein C and S
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What is the mechanism of Warfarin?
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Warfarin inhibits the enzyme vitamin K epoxide reductase
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Why do neonates require Vitamin K injections when they are born?
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- Neonates lack enteric bacteria, which produce vitamin K
- Vitamin K is necessary for maturing coagulation cascade components |
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What are the implications of a Vitamin K deficiency?
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↓ Synthesis of factors II, VII, IX, X, protein C, and protein S
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What carries / protects Factor VIII?
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von Willebrand Factor
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What is the action of Protein C?
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Cleaves and inactivates factors Va and VIIIa
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How does Protein C get activated to exert its inactivating effects on Factors Va and VIIIa?
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- Protein C converted to Activated Protein C via thrombin-thrombomodulin complex (on endothelial cells)
- Protein S helps allow activated Protein C to exert its effects |
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What happens in fibrinolysis?
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- Cleavage of fibrin mesh
- Destruction of coagulation factors |
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What mediates fibrinolysis?
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Plasminogen activation to Plasmin mediates Fibrinolysis
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What medication can help activate Plasminogen to Plasmin? Utility?
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tPA - used as a thrombolytic
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What is the action of Antithrombin?
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Inhibits activated forms of factor II, VII, IX, X, XI, and XII
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What is the action of Heparin?
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Heparin enhances the activity of antithrombin; antithrombin inhibits activated forms of factor II, VII, IX, X, XI, and XII
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What are the principal targets of antithrombin?
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Thrombin and Factor Xa
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What is the effect of the Factor V Leiden mutation?
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Produces a factor V resistant to inhibition by activated Protein C
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What are the steps of platelet plug formation (primary hemostasis)?
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1. Injury
2. Adhesion 3. Activation 4. Aggregation |
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What is the first step of platelet plug formation (primary hemostasis)?
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Injury
- vWF binds to exposed collagen upon endothelial damage |
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What is the second step of platelet plug formation (primary hemostasis), after injury?
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Adhesion:
- Platelets bind vWF via GpIb receptor at the site of injury only (specific) - Platelets release ADP and Ca2+ (necessary for coagulation cascade) - ADP helps platelet adhere to endothelium |
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What is the third step of platelet plug formation (primary hemostasis), after adhesion?
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Activation
- ADP binding to receptor induces GpIIb/IIIa expression at platelet surface |
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What is the fourth step of platelet plug formation (primary hemostasis), after activation?
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Aggregation
- Fibrinogen binds GpIIb/IIIa receptors and links platelets - Temporary plug stops bleeding |
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What are the pro-aggregation factors?
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- TXA2 (released by platelets)
- ↓ Blood flow - ↑ Platelet aggregation |
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What are the anti-aggregation factors?
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- PGI2 and NO (released by endothelial cells)
- ↑ Blood flow - ↓ Platelet aggregation |
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What is the mechanism of aspirin?
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Inhibits cyclooxygenase (TXA2 synthesis)
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What is the mechanism of ticlopidine?
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Inhibits ADP-induced expression of GpIIb/IIIa
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What is the mechanism of clopidogrel?
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Inhibits ADP-induced expression of GpIIb/IIIa
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What is the mechanism of abciximab?
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Inhibits GpIIb/IIIa directly
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What is the mechanism of ristocetin?
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Activates vWF to bind to GpIb
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What is useful for diagnosis of von Willebrand disease?
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Normal platelet aggregation response is not seen in von Willebrand disease
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What disease occurs if there is a deficiency of GpIb?
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Bernard-Soulier Syndrome
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What disease occurs if there is a deficiency of GpIIb/IIIa?
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Glanzmann Thombasthenia
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What molecules are inside of endothelial cells?
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- vWF
- Thromboplastin - tPA and PGI2 |
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What can acute phase reactants in the plasma lead to?
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RBC aggregation, thereby ↑ RBC sedimentation rate (RBC aggregates have a higher density than plasma)
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What causes an increased erythrocyte sedimentation rate (ESR)?
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- Infections
- Autoimmune diseases (SLE, rheumatoid arthritis, temporal arteritis) - Malignant neoplasms - GI disease (ulcerative colitis) - Pregnancy |
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What causes a decreased erythrocyte sedimentation rate (ESR)?
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- Polycythemia
- Sickle cell anemia - CHF - Microcytosis - Hypofibrinogenemia |
