CH2.txt

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CH2.txt
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  1. What does inflammation allow?
    Allows inflammatory cells, plasma proteins (e.g., complement), and fluid to exit blood vessels and enter the interstitial space
  2. Inflammation is divided into what?
    Divided into acute and chronic inflammation
  3. What is inflammation characterized by?
    the presence of edema and neutrophils in tissue
  4. Inflammation arises in response to what?
    infection (to eliminate pathogen) or tissue necrosis (to clear necrotic debris)
  5. innate immunity
    Immediate response with limited specificity
  6. What are the mediators of acute inflammation?
    Toll-like receptors, Arachidonic acid (AA) metabolites, Mast cells, Complement, Hageman Factor
  7. Toll-like receptors
    Present on cells of the innate immune system (e.g., macrophages and dendritic cells)
  8. How are TLRs attivated?
    pathogen-associated molecular patterns (PAMPs) that are commonly shared by microbes, CD14 (a TLR) on macrophages recognizes lipopolysaccharide (a PAMP) on the outer membrane of gram-negative bacteria
  9. TLR activation results in what?
    upregulation of NF-kB, a nuclear transcription factor
  10. What does NF-kB do?
    activates immune response genes leading to production of multiple immune mediators
  11. TLRs and chronic inflammation?
    They are also present on cells of adaptive immunity (e.g., lymphocytes) and play an important role in mediating chronic inflammation.
  12. Arachidonic acid (AA) metabolites
    1. AA is released from the phospholipid cell membrane by phospholipase A2 and then acted upon by cyclooxygenase or 5-lipoxygenase.
  13. Cyclooxygenase
    produces prostaglandins (PG) a. PGI2, PGD2 and PGE2 mediate vasodilation and increased vascular permeability. PGE2 also mediates pain.
  14. 5-lipoxygenase
    produces leukotrienes (LT) a. LTB4 attracts and activates neutrophils. b. LTC4, LTD4 and LTE4 (slow reacting substances of anaphylaxis) mediate vasoconstriction, broncho spasm, and increased vascular permeability.
  15. Where are Mast cells located?
    1. Widely distributed throughout connective tissue
  16. How are Mast cells activated?
    (1) tissue trauma (2) complement proteins C3a and C5a (3) cross-linking of cell-surface IgE by antigen
  17. Mast cells immediate response is?
    involves the release of preformed histamine granules, which mediate vasodilation of arterioles and increased vascular permeability
  18. Mast cells delayed response is?
    involves production of arachidonic acid metabolites, particularly leukotrienes.
  19. Complement
    proinflammatory serum proteins that complement inflammation
  20. Where is complement located?
    Circulate as inactive precursors;
  21. Activation of complement occurs via what?
    Classical pathway, Alternative pathway, MBL pathway
  22. Classical pathway
    C1 binds IgG or IgM that is bound to antigen
  23. Alternative pathway
    Microbial products directly activate complement.
  24. Mannose binding lectin pathway
    mannose binding lectin (MBL) pathway MBL binds to mannose on microorganisms and activates complement
  25. All pathways of complement result in?
    production of C3 convertase (mediates C3—>C3a and C3b, producing C5 convertase (mediates C5—>C5a and C5b)
  26. What forms the MAC?
    C5b complexes with C6-C9 to form the membrane attack complex (MAC)
  27. C3a and C5a
    (anaphylatoxins)—trigger mast cell degranulation, resulting in histamine-mediated vasodilation and increased vascular permeability
  28. C5a
    chemotactic for neutrophils
  29. C5b
    opsonin for phagocytosis
  30. MAC
    Lyses microbes by creating a hole in the cell membrane
  31. Where is Hageman factor (Factor XII) produced?
    Inactive proinflammatory protein produced in liver
  32. How is Hageman factor (Factor XII)?
    Activated upon exposure to subendothelial or tissue collagen;
  33. Hageman factor (Factor XII) activates what?
    1. Coagulation and fibrinolytic systems 2. Complement 3. Kinin system
  34. Kinin system
    Kinin cleaves high-molecular-weight kininogen (HMWK) to bradykinin, which mediates vasodilation and increased vascular permeability (simitar to histamine), as well as pain.
  35. What are the cardinal signs of inflammation?
    Redness (rubor) and warmth (calor), swelling, pain, fever
  36. What is Redness (rubor) and warmth (calor) due to?
    1. Due to vasodilation, which results in increased blood flow
  37. How does Redness (rubor) and warmth (calor) occur?
    Occurs via relaxation of arteriolar smooth muscle;
  38. Key mediators of Redness (rubor) and warmth (calor) are?
    histamine, prostaglandins, and bradykinin
  39. Swelling (tumor) is due to what?
    Due to the leakage of fluid from postcapillary venules into the interstitial space (exudate)
  40. What are the Key mediators of swelling?
    (1) histamine, which causes endothelial cell contraction and (2) tissue damage, resulting in endothelial cell disruption,
  41. Pain (dolor)
    Bradvkinin and PGE2 sensitize sensory nerve endings.
  42. Fever
    1. Pyrogens (e.g., LPS from bacteria) cause macrophages to release IL-1 and TNF, which increase cyclooxygenase activity in perivascular cells of the hypothalamus, 2. Increased PGE2 raises temperature set point.
  43. What are the steps in neutrophil arrival?
    Margination, Rolling, Adhesion, Transmigration and Chemotaxis, Phagocytosis, Destruction of phagocytosed material, resolution
  44. Step 1—Marginatum
    1. Vasodilation slows blood flow in postcapillary venules. 2. Cells marginate from center of flow to the periphery.
  45. Step 2—Rolling
    1. Selectin speed bumps are upregulaled on endothelial cells. 2. Selectins bind sialyl Lewis X on leukocytes. 3. Interaction results in rolling of leukocytes along vessel wall
  46. P-selectin is released from where and what does it mediate?
    release from Weibel Palade bodies, is mediated by histamine.
  47. E-selectin is induced by what?
    TNF and IL-1.
  48. Step 3—Adhesion
    1. Cellular adhesion molecules (ICAM and VCAM) are upregulated on endothelium by TNF and IL-1 2. Integrins are upregulated on leukocytes by C5a and LTB4 3. Interaction between CAMs and integrins results in firm adhesion of leukocytes to the vessel wall
  49. Leukocyte adhesion deficiency
    is most commonly due to an autosomal recessive defect of integrins (CD18 subunit)
  50. What are the clinical features of LAD?
    delayed separation of the umbilical cord, increased circulating neutrophils (due to impaired adhesion of marginated pool of leukocytes), and recurrent bacterial infections that lack pus formation.
  51. Step 4—Transmigration and Chemotaxis
    1. Leukocytes transmigrate across the endothelium of postcapillary venules and move toward chemical attractants (chemotaxis).
  52. Neutrophils are attracted by
    bacterial products, IL-8, C5a, and LTB4
  53. Step 5—Phagocytosis
    1. Consumption of pathogens or necrotic tissue; phagocytosis is enhanced by opsonins (IgG and C3a). 2. Pseudopods extend from leukocytes to form phagosomes, which are internalized and merge with lysosomes to produce phagolysosomes.
  54. Chediak-Higashi syndrome
    is a protein trafficking defect (autosomal recessive) characterized by impaired phagolysosome formation.
  55. Clinical features of Chediak-Higashi syndrome include
    Increased risk of pyogenic infections, Neutropenia, Giant granules in leukocytes, Defective primary hemostasia, Albinism, Peripheral neuropathy
  56. Why is there Neutropenia in Chediak Higashi syndrome?
    (due to intramedullary death of neutrophils)
  57. In chediak higashi there are Giant granules in leukocytes because?
    due to fusion of granules arising from the Golgi apparatus
  58. In chediak higashi Defective primary hemostasia is due to?
    abnormal dense granules in platelets
  59. Step 6—Destruction of phagocytosed material
    1. O2-dependent killing is the most effective mechanism. 2. HOCl generated by oxidative burst in phagolysosomes destroys phagocytosed microbes.
  60. How does O2 dependant killing occur?
    O2 is converted to O2. by NADPH oxidase (oxidative burst). O2. is converted to H202, by superoxide dismutase (SOD). H202 is converted to HOCl (bleach) by myeloperoxidase (MPO).
  61. NADPH oxidase
    O2 is converted to O2. by (oxidative burst).
  62. SOD
    O2. is converted to H202, by superoxide dismutase
  63. MPO
    H202 is converted to HOCl (bleach) by myeloperoxidase (MPO).
  64. CGD is characterized by?
    poor O2-dependent killing.
  65. CGD is Due to?
    NADPH oxidase defect (X-linked or autosomal recessive)
  66. What does CGD lead to?
    recurrent infection and granuloma formation with catalase-positive organisms, particularly Staphylococcus aureus, Pseudpmonas cepacia, Serratia marcescens, Nocardia, and Aspergillus
  67. Nitrobiue tetrazolium test
    is used to screen for CGD. Leukocytes are incubated with NBT dye, which turns blue if NADPH oxidase can convert 02 to O2. but remains colorless if NADPH oxidase is defective.
  68. MPO deficiency results in?
    defective conversion of H202 to HOCl
  69. MPO deficiency symptoms?
    Increased risk for Candida infections; however, most patients are asymptomatic.
  70. MPO deficiency and NBT?
    normal; respiratory burst O2. to H2O2 is intact.
  71. O2-independent killing
    less effective than O2-dependent killing and occurs via enzymes present in leukocyte secondary granules (e.g., lysozyme in macrophages and major basic protein in eosinophils).
  72. Step 7—Resolution
    Neutrophils undergo apoptosis and disappear within 24 hours after resolution of the inflammatory stimulus.
  73. Macrophages
    Macrophages predominate after neutrophils and peak 2-3 days after inflammation begins.
  74. What are macrophages derived from?
    monocytes in blood
  75. How do macrophages arrive in tissue?
    via the margination, rolling, adhesion, and transmigration sequence
  76. What do macrophages do?
    Ingest organisms via phagocytosis (augmented by opsonins) and destroy phagocytosed material using enzymes (e.g., lysozyme) in secondary granules (02-independent killing)
  77. What are the outcomes for macrophages managing the next step of the inflammatory process?
    Resolution and healing, 2. Continued acute inflammation, Abscess, Chronic inflammation
  78. Macrophages induce Resolution and healing by?
    Anti-inflammatory cytokines (1L-10 and TGF-(Beta) are produced by macrophages.
  79. Macrophages induce Continued acute inflammation by?
    persistent pus formation; IL-8 from macrophages recruits additional neutrophils.
  80. Macrophages induce Abscess by?
    acute inflammation surrounded by fibrosis; macrophages mediate fibrosis via fibrogenic growth factors and cytokines.
  81. Macrophages induce chronic inflammation by?
    Macrophages present antigen to activate CD4+ helper T cells, which secrete cytokines that promote chronic inflammation
  82. Chronic inflammation is characterized by?
    presence of lymphocytes and plasma cells in tissue, its a delayed response but more specific (adaptive immunity) than acute inflammation
  83. Chronic inflammation stimuli include
    (1) persistent infection (most common cause); (2) infection with viruses, mycobacteria, parasites, and fungi; (3) autoimmune disease; (4) foreign material; and (5) some cancers.
  84. T lymphocytes are produced where?
    Produced in bone marrow as progenitor T cells
  85. Where are T lymphocytes further developed?
    Further develop in the thymus where the T-cell receptor (TCR) undergoes rearrangement and progenitor cells become CD4+ helper T cells or CD8 cytotoxic T cells
  86. T cells use TCR complex for?
    (TCR and CD3) for antigen surveillance
  87. What does the TCR complex do?
    recognizes antigen presented on MHC molecules i. CD4+ T cells—MHC class II, CD8+ T cells—MHC class I
  88. Activation of T cells requires what?
    (1) binding of antigen/MHC complex and (2) an additional 2nd signal.
  89. CD4+ helper T-cell activation
    Extracellular antigen (e.g., foreign protein) is phagocytosed, processed, and presented on MHC class II, which is expressed by antigen presenting cells (APCs) - B7 on APC binds CD28 on CD4+ helper T cells providing 2nd activation signal.
  90. Activated CD4+ helper T cells do what?
    secrete cytokines that help inflammation and are divided into two subsets.
  91. What are the subsets of activated CD4+?
    TH1 and TH2
  92. TH1 subset
    secretes IL-2 (T cell growth factor and CD8+ T cell activator) and IFN-gamma (macrophage activator)
  93. TH2 subset
    IL-4, IL-5, IL-10
  94. TH2 subset secretes IL-4 which results in?
    facilitates B-cell class switching to IgG and IgE
  95. TH2 subset secretes IL-5 which results in?
    eosinophil chemotaxis and activation, maturation of B cells to plasma cells, and class switching to IgA
  96. TH2 subset secretes IL-10 which?
    inhibits TH1 phenotype
  97. How does CD8+ cytotoxic T-cell activation occur?
    Intracellular antigen (derived from proteins in the cytoplasm) is processed and presented on MHC class I, which is expressed by all nucleated cells and platelets.
  98. What provides the 2nd activation signal for CD8+?
    IL-2 from CD4+ TH1 cell
  99. Cytotoxic T cells are activated for?
    killing
  100. Cytotoxic T cell killing occurs via
    Secretion of perforin and granzyme; perforin creates pores that allow granzyme to enter the target cell, activating apoptosis. Expression of FasL, which binds Fas on target cells, activating apoptosis
  101. B Lymphocytes
    Immature B cells are produced in the bone marrow and undergo immunoglobulin rearrangements to become naive B cells that express surface IgM and IgD.
  102. B-cell activation occurs via
    Antigen binding by surface IgM or IgD; results in maturation to IgM or IgD secreting plasma cells, B-cell antigen presentation to CD4+ helper T cells via MHC class II
  103. What provides the 2nd activation signal
    CD40 receptor on B cell binds CD40L on helper T cell
  104. What happens after the 2nd activation of B cells?
    Helper T cell then secretes IL-4 and IL-5 (mediate B-cell isotype switching, hypermutation, and maturation to plasma cells)
  105. What is granulomatous inflammation?
    Subtype of chronic inflammation, Characterized by granuloma, which is a collection of epithelioid histiocytes
  106. What are epithelioid histiocytes?
    macrophages with abundant pink cytoplasm, usually surrounded by giant cells and a rim of lymphocytes
  107. What is granulomatous inflammation divided into?
    noncaseating and caseating subtypes
  108. What is noncaseating granulomas?
    lack central necrosis
  109. Common etiologies for noncaseating granulomas?
    include reaction to foreign material, sarcoidosis, beryllium exposure, Crohn disease, and cat scratch disease,
  110. Caseating granulomas
    exhibit central necrosis and are characteristic of tuberculosis and fungal infections
  111. What are the seps involved in granuloma formation?
    1. Macrophages process and present antigen via MHC class II to CD4+ helper T cells. 2. Interaction leads macrophages to secrete IL-12, inducing CD4+ helper T cells to differentiate into THl subtype. 3. TH1 cells secrete IFN-y, which converts macrophages to epithelioid histiocytes and giant cells.
  112. What is DiGeorge Syndrome?
    Developmental failure of the third and fourth pharyngeal pouches
  113. What is DiGeorge Syndrome?
    Due to 22qll microdeletion
  114. What does DiGeorge Syndrome presents with?
    T-cell deficiency (lack of thymus); hypocalcemia (lack of parathyroids); and abnormalities of heart, great vessels, and face
  115. Severe combined immunodeficiency
    defective cell-mediated and humoral immunity
  116. What are the etiologies for SCID?
    Cytokine receptor defects, Adenosine deaminase (ADA) deficiency, MHC class II deficiency
  117. Cytokine receptor defects
    Cytokine signaling is necessary for proliferation and maturation of B and T cells.
  118. Adenosine deaminase (ADA) deficiency
    ADA is necessary to deaminate adenosine and deoxyadenosine for excretion as waste products; buildup of adenosine and deoxyadenosine is toxic to lymphocytes
  119. MHC class II deficiency
    MHC class II is necessary for CD4+ helper T cell activation and cytokine production
  120. SCID is characterized by?
    susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines
  121. SCID treatment is?
    sterile isolation ('bubble baby ) and stem cell transplantation.
  122. What is X-Linked agammaglobulinemia?
    Complete lack of immunoglobulin due to disordered B-cell maturation, naive B cells cannot mature to plasma cells.
  123. What is X-Linked agammaglobulinemia due to?
    mutated Bruton tyrosine kinase; X-linked
  124. How does X-Linked agammaglobulinemia present?
    after 6 months of life with recurrent bacterial, enterovirus (e.g., polio and coxsackievirus), and Giardia lamblia infections; maternal antibodies present during the first five months of life are protective.
  125. What is the caveat associated with X-Linked agammaglobulinemia?
    Live vaccines (e.g., polio) must be avoided.
  126. What is common variable immunodeficiency?
    Low immunoglobulin due to B-cell or helper T-cell defects
  127. CVID increases the risk of what?
    increased risk for bacterial, enterovirus, and Giardia lamblia infections, usually in late childhood, Increased risk for autoimmune disease and lymphoma
  128. IgA deficiency
    Low serum and mucosal IgA; most common immunoglobulin deficiency
  129. IgA deficiency increases the risk for?
    Increased risk for mucosal infection, especially viral; however, most patients are asymptomatic.
  130. Hyper IgM syndrome
    Characterized by elevated IgM, Due to mutated CD40L (on helper T cells) or CD40 receptor (on B cells)
  131. What is the effect of the mutation leading to hyper-IgM?
    Second signal cannot be delivered to helper T cells during B-cell activation so cytokines necessary for immunoglobulin class switching are not produced
  132. No class switching in hyper IgM syndrome leads to what?
    Low IgA, IgG, and IgE result in recurrent pyogenic infections (due to poor opsonization), especially at mucosal sites.
  133. What is Wiscott Aldrich syndrome?
    Characterized by thrombocytopenia, eczema, and recurrent infections {defective humoral and cellular immunity)
  134. What is Wiscott Aldrich syndrome due to?
    mutation in the WASP gene; X-linked
  135. What are the Complement Deficiencies?
    C5-C9 deficiencies, CI inhibitor deficiency
  136. C5-C9 deficiencies
    increased risk for Neisseria infection (Ngonorrhoeae and N meningitidis)
  137. CI inhibitor deficiency
    results in hereditary angioedema, which is characterized by edema of the skin (especially periorbital, Fig. 2.3) and mucosal surfaces
  138. Autoimmune disorders are characterized by?
    immune-mediated damage of tissues, 1% prevalence in the US, Involves loss of self-tolerance
  139. In autoimmune disorders what does loss of self tolerance involve
    Self-reactive lymphocytes are regularly generated but undergo apoptosis (negative selection) in the thymus (T cells) or bone marrow (B cells) or become anergic (due to recognition of antigen in peripheral lymphoid tissues with no 2nd signal).
  140. Autoimmune disease is more common in?
    women; classically affects women of childbearing age
  141. What is the etiology for autoimmune disease?
    It is likely an environmental trigger in genetically susceptible individuals (increased incidence in twins and associated with certain HLA subtypes).
  142. What is systemic Lupus Erythematosus?
    Systemic autoimmune disease, antibodies against tbe host damage multiple tissues via type II (cytotoxic) and type III (antigen-antibody complex) hypersensitivity.
  143. Systemic Lupus Erythematosus is more common in?
    women, especially African American females
  144. Clinical features of systemic Lupus Erythematosus include?
    • Fever and weight loss
    • Malar 'butterfly' rash (especially upon exposure to sunlight)
    • Arthritis
    • Pleuritis and pericarditis (involvement of serosal surfaces)
    • CNS psychosis
    • Renal damage
    • Endocarditis, myocarditis, or pericarditis (can affect any layer of the heart)
    • Anemia, thrombocytopenia, or leukopenia (due to autoantibodies against cell surface proteins)
    • Renal failure and infection are common causes of death
  145. Anemia, thrombocytopenia, or leukopenia in SLE is due to?
    autoantibodies against cell surface proteins
  146. Most common causes of death in SLE?
    Renal failure and infection
  147. What is a classic finding for systemic lupus eythematosus?
    Libman-Sacks endocarditis is and is characterized by small, sterile deposits on both sides of the mitral valve.
  148. What is the most common clinical features of systemic Lupus Erythematosus?
    Diffuse proliferative glomerulonephritis, though other patterns of injury also occur.
  149. Systemic Lupus Erythematosus and anemia, thrombocytopenia, or leukopenia is due to?
    autoantibodies against cell surface proteins
  150. What are common causes of death for SLE?
    renal failure and infection
  151. SLE is characterized by
    antinudear antibody ANA; sensitive, but not specific and anti dsDNA antibodies (highly specific)
  152. Antihistone antibody is characteristic of?
    drug-induced SLE.
  153. What are some common causes of drug induced SLE?
    1. Hydralazine, procainamide, and isoniazid are common causes 2. Removal of drug usually results in remission.
  154. 30% of what cases are associated with SLE?
    Antiphospholipid antibody syndrome
  155. Antiphospholipid antibody syndrome is characterized by?
    autoantibody against proteins bound to phospholipids. 2.
  156. In antiphospholipid antibody syndrome what are the most common antibodies?
    Anticardiolipin and lupus anticoagulant
  157. In antiphospholipid antibody syndrome what tests are disrupted?
    Leads to false-positive syphilis test and falsely-elevated PTT lab studies, respectively
  158. What does antiphospholipid antibody syndrome result in?
    arterial and venous thrombosis including deep venous thrombosis, hepatic vein thrombosis, placental thrombosis (recurrent pregnancy loss), and stroke
  159. What does antiphospholipid antibody syndrome require?
    lifelong anticoagulation
  160. What is sjogren syndrome?
    Autoimmune destruction of lacrimal and salivary glands, lymphocyte-mediated damage (type IV hypersensitivity) with fibrosis
  161. How does sjogren syndrome classically present?
    as dry eyes (keratoconjunctivitis), dry mouth (xerostomia), and recurrent dental carries in an older woman (50-60 years)—Can't chew a cracker, dirt in my eyes
  162. Sjogren syndrome is characterized by?
    ANA and anti-ribonucleoprotein antibodies anti-SS-A/Ro and anti-SS-B/La)
  163. Sjogren syndrome is often associated with?
    other autoimmune diseases, especially rheumatoid arthritis
  164. Sjogren syndrome results in increased risk for?
    B-cell (marginal zone) lymphoma, which presents as unilateral enlargement of the parotid gland late in disease course
  165. Scleroderma is
    Autoimmune tissue damage with activation of fibroblasts and deposition of collagen (fibrosis)
  166. Scleroderma is divided into?
    diffuse and localized types
  167. Diffuse type of scleroderma exhibits?
    skin and early visceral involvement.
  168. Scleroderma involves
    Almost any organ can be involved; esophagus is commonly affected, resulting in disordered motility (dysphagia for solids and liquids).
  169. Scleroderma is characterized by?
    ANA and anti-DNA topoisomerase I (Scl-70) antibody
  170. Scleroderma localized type exhibits?
    local skin and late visceral involvement.
  171. What is CREST syndrome?
    For localized type scleroderma: Calcinosis/anti-Centroniere antibodies, Raynaud phenomenon. Esophageal dysmotility, Sclerodactyly, and Telangiectasias of the skin.
  172. What is mixed connective tissue disease?
    autoimmune-mediated tissue damage with mixed features of SLE, systemic sclerosis, and polymyositis
  173. What is mixed connective tissue disease characterized by?
    serum antibodies against U1 ribonucleoprotein
  174. When is healing initiated?
    when inflammation begins.
  175. Wound healing occurs via?
    a combination of regeneration and repair
  176. In wound healing regeneration occurs via?
    Replacement of damaged tissue with native tissue; dependent on regenerative capacity of tissue
  177. Tissues are divided into three types based on?
    regenerative capacity: labile, stable, and permanent.
  178. Labile tissues
    possess stem cells that continuously cycle to regenerate the tissue.
  179. Examples of Labile tisues
    1. Small and large bowel (stem cells in mucosal crypts) 2. Skin (stem cells in basal layer) 3. Bone marrow (hematopoietic stem cells)
  180. Stable tissues are
    comprised of cells that are quiescent G0, but can reenter the cell cycle to regenerate tissue when necessary.
  181. What is a classic example of regeneration?
    In the liver by compensatory hyperplasia after partial resection. Each hepatocyte produces additional cells and then reenters quiescence.
  182. Permanent tissues
    lack significant regenerative potential (myocardium, skeletal muscle, and neurons).
  183. Repair
    Replacement of damaged tissue with fibrous scar, Occurs when regenerative stem cells are lost (e.g., deep skin cut) or when a tissue lacks regenerative capacity (e.g., healing after a myocardial infarction
  184. Granulation tissue
    Its formation is the initial phase of repair
  185. In the initial phase of repair what does the fibroblasts do?
    deposit type III collagen
  186. In the initial phase of repair what does the capillaries do?
    provide nutrients
  187. Granulation tissue consists of?
    fibroblasts (deposit type III collagen), capillaries (provide nutrients), and myofibroblasts (contract wound)
  188. Granulation tissue eventually results in?
    scar formation, in which type 111 collagen is replaced with type 1 collagen
  189. Type III collagen is
    pliable and present in granulation tissue, embryonic tissue, uterus, and keloids.
  190. Type I collagen
    has high tensile strength and is present in skin, bone, tendons, and most organs,
  191. Collagenase
    removes type 111 collagen and requires zinc as a cofactor.
  192. Tissue regeneration and repair is mediated by?
    paracrine signaling via growth factors (e.g macrophages secrete growth factors that target fibroblasts)
  193. What results in gene expression and cellular growth?
    Interaction of growth factors with receptors (e.g.. epidermal growth factor with growth factor receptor)
  194. Examples of mediators of tissue repair and regeneration
    TGF-alpha, TGF-beta, platelet, fibroblast growth factor, VEGF
  195. TGF-alpha
    epithelial and fibroblast growth factor
  196. TGF-beta
    important fibroblast growth factor; also inhibits inflammation
  197. Platelet-derived growth factor
    growth factor for endothelium, smooth muscle, and fibroblasts
  198. Fibroblast growth factor
    important for angiogenesis; also mediates skeletal development
  199. Vascular endothelial growth factor (VEGF)
    important for angiogenesis
  200. Cutaneous healing occurs via
    primary or secondary intention.
  201. Primary intention
    Wound edges are brought together (e.g., suturing of a surgical incision); leads to minimal scar formation
  202. Secondary intention
    Edges are not approximated. Granulation tissue fills the defect; myofibroblasts then contract the wound, forming a scar.
  203. Delayed wound healing occurs in
    1. Infection (most common cause; S aureus is the most common offender)
  204. Vitamin C is
    an important cofactor in the hydroxylation of proline and lysine procollagen residues; hydroxylation is necessary for eventual collagen cross-linking.
  205. What is necessary for the formation of stable collagen?
    Copper is a cofactor forlysyl oxidase, which cross-links lysine and hydroxy lysine to form stable collagen.
  206. What is a cofactor for collagenase?
    Zinc which replaces the type III collagen of granulation tissue with stronger type I collagen
  207. What are some causes for delayed wound healing?
    foreign body, ischemia, diabetes, and malnutrition,
  208. Dehiscence is
    rupture of a wound; most commonly seen after abdominal surgery
  209. Hypertrophic scar is
    excess production of scar tissue that is localized to the wound
  210. Keloid is
    excess production of scar tissue that is out of proportion to the wound
  211. Keloid is characterized by
    excess type III collagen
  212. Keloid genetic predisposition
    more common in African Americans
  213. Keloid classically affects
    earlobes, face, and upper extremities

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