Ch 2 - Inflammation, Inflammatory Disorders, and Wound Healing Flashcards
1
Q
ACUTE INFLAMMATION is characterized by
A
Presence of EDEMA and NEUTROPHILS
2
Q
Conditions in which ACUTE INFLAMMATION arises
A
Response to INFECTION to eliminate pathogen and TISSUE NECROSIS to clear necrotic debris
3
Q
Acute inflammation in MYOCARDIAL INFARCTION
A
24hrs post-MI there is acute inflammation with NEUTROPHILS to clear necrotic debris –> causes increased WBCs post-MI (mainly neutrophils)
4
Q
Key HALLMARK 24hrs post-MI
A
Acute inflammation with NEUTROPHILS
5
Q
Acute Inflammation: innate vs adaptive immunity
A
INNATE - immediate response with limited specificity
6
Q
How do MACROPHAGES recognize GRAM NEGATIVE BACTERIA?
A
CD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteriaCD14 (a TLR) on MACROPHAGES recognizes LPS (a pathogen assoc molecular pattern - PAMP) on Gram neg bacteria
7
Q
Result of TLR activation
A
Upregulation of NF-kB which activates immune response genes –> production of multiple immune mediators
8
Q
Cells involved in INNATE IMMUNITY
A
Mast cells, macrophages, neutrophils, eosinophils, basophils, epithelium on body surfaces, mucous secreted by cells, complement system
9
Q
Cells involved in ADAPTIVE IMMUNITY
A
lymphocytes, T cells and Ab - very specific target
10
Q
Arachidonic acid –> PGs
A
AA released from phospholipid membrane by phospholipase A2 and acted upon by COX –> PGs
11
Q
Arachidonic acid –> Leukotrienes (LT)
A
AA released from phospholipid membrane by phospholipase A2 and acted upon by 5-lipoxygenase –> LTs
12
Q
PGs that mediate VASODILATION and INCREASED VASCULAR PERMEABILITY
A
PGI2, PGD2, PGE2
13
Q
Function of PGE2
A
Mediates PAIN, fEver as well as VASODILATION and INCREASED PERMEABILITY
14
Q
In inflammation, VASODILATION occurs at the level of:
A
ARTERIOLE
15
Q
In inflammation, increased VASCULAR PERMEABILITY occurs at:
A
POST-CAPILLARY VENULE
16
Q
Which LEUKOTRIENE ATTRACTS NEUTROPHILS?
A
LTB4
17
Q
Chemical Mediators that ATTRACT NEUTROPHILS?
A
LTB4, C5a, IL-8, Bacterial products
18
Q
Leukotrienes that MEDIATE VASOCONSTRICTION, BRONCHOSPASM, and INCREASED VASCULAR PERMEABILITY
A
LTC4, LTD4, LTE4 - cause smooth muscle to contract
19
Q
SLOW reacting substances of ANAPHYLAXIS
A
LTC4, LTD4, LTE4 - vasoconstriction, bronchospasm, increased vascular permeability
20
Q
What ACTIVATES MAST CELLS?
A
Tissue trauma, C3a & C5a, cross-linking of surface IgE by Ag
21
Q
IMMEDIATE RESPONSE of MAST cells?
A
Release of preformed HISTAMINE - mediates VASODILATION (of ARTERIOLES) and INCREASED VASCULAR PERMEABILITY (at post-cap venules)
22
Q
DELAYED RESPONSE of MAST cells?
A
Production of AA metabolites - particularly LEUKOTRIENES - maintain acute inflamm
23
Q
Activation of Complement Pathway
A
Classical, Alternative Pathway, Mannose-binding lectin pathway - all pathways result in production of C3 CONVERTASE
24
Q
Activation of CLASSICAL Complement Pathway
A
GM makes CLASSIC cars - C1 binds IgG or IgM that is bound to Ag
25
COMPLEMENT proteins that TRIGGER MAST CELL DEGRANULATION
C3a and C5a - anaphylatoxins - result in histamine mediated vasodilation and increased vascular permeability
26
COMPLEMENT protein that is CHEMOTACTIC for NEUTROPHILS
C5a
27
COMPLEMENT protein that acts as OPSONIN for phagocytes
C3b (also IgG)
28
COMPLEMENT proteins that make up MAC?
C5b, C6-9
29
Function of Membrane Attack Complex
lyses microbes by creating a hole in the cell membrane
30
What activates HAGEMAN FACTOR (Factor XII)?
inactive proinflamm protein produced in liver that is activated upon exposure to subendothelial or tissue collagen
31
HAGEMAN FACTOR (Factor XII) activates which processes?
COAGULATION and FIBRINOLYTIC systems --\> DIC; complement; Kinin system - produces BRADYKININ (mediates VASODILATION, INCREASED VASCULAR PERMEABILITY, and PAIN)
32
Which chemical proteins mediate PAIN?
PGE2 and BRADYKININ
33
Pathophys of GRAM NEGATIVE SEPSIS --\> DIC
GRAM NEG organisms have ability to ACTIVATE HAGEMAN FACTOR which activates COAGULATION and FIBRINOLYTIC systems
34
Primary mediator of REDNESS (rubor) and WARMTH (calor) in inflammation
HISTAMINE; also PGs and bradykinin - vasodilation (relaxation of arteriolar smooth muscle)
35
Primary mediator of SWELLING (tumor) in inflammation
HISTAMINE; also tissue damage - cause endothelial cell contaction --\> leakage of fluid from postcap venule
36
Primary mediators of PAIN (dolor) in inflammation
BRADYKININ and PGE2 - sensitive nerve endings
37
Primary mediator of FEVER in inflammation
PGE2 raises temp set point - MACROPHAGES release IL-1 and TNF which increase COX activity in perivascular cells of the HYPOTHALAMUS
38
Steps of NEUTROPHIL arrival and function
Margination --\> Rolling --\> Adhesion --\> Transmigration and Chemotaxis --\> Phagocytosis --\> Destruction of phagocytosed material --\> Resolution
39
How do LEUKOCYTES ROLL on Endothelial cells?
P-selectin and E-selectin bind SIALYL LEWIS X on leukocytes
40
P-SELECTIN
Released from WEIBEL-PALADE bodies - mediated by HISTAMINEReleased from WEIBEL-PALADE bodies - mediated by HISTAMINEReleased from WEIBEL-PALADE bodies - mediated by HISTAMINEReleased from WEIBEL-PALADE bodies - mediated by HISTAMINEReleased from WEIBEL-PALADE bodies - mediated by HISTAMINEReleased from WEIBEL-PALADE bodies - mediated by HISTAMINEReleased from WEIBEL-PALADE bodies - mediated by HISTAMINEReleased from WEIBEL-PALADE bodies - mediated by HISTAMINE
41
Weibel-Palade bodies release:
von Willebrand factor and P-selectin von Willebrand factor and P-selectin von Willebrand factor and P-selectin von Willebrand factor and P-selectin von Willebrand factor and P-selectin von Willebrand factor and P-selectin von Willebrand factor and P-selectin von Willebrand factor and P-selectin
42
How does LEUKOCYTE ADHERE to endothelial cell?
INTEGRINS on leukocytes bind to ICAM and VCAM on endothelium
43
What upregulates ICAM and VCAM?
TNF and IL-1
44
What upregulates INTEGRINS on leukocytes?
C5a and LTB4 (both chemotactic for neutrophils as well)
45
LEUKOCYTE ADHESION DEFICIENCY (LAD)
AR defect of INTEGRINS (CD 18 subunit)
46
Clinical Features of Leukocyte Adhesion Deficiency
DELAYED SEPARATION OF UMBILICAL CORD (acute inflamm cannot cross endothelium to clear tissue), INCREASED CIRCULATING NEUTROPHILS (1/2 of body's neutrophils typically hang out in blood vessels in lungs but with less adhesion --\> more circulating), and RECURRENT BACTERIAL INFECTIONS THAT LACK PUS (pus is dead neutrophils in fluid and they can't cross so no pus)
47
Where do LEUKOCYTES TRANSMIGRATE across ENDOTHELIUM?
POST-CAPILLARY VENULE
48
CHEDIAK-HIGASHI SYNDROME
AR Protein Trafficking Defect --\> IMPAIRED PHAGOLYSOSOME FORMATION; railroad (microtubules) that lead from phagosome to lysosome is out
49
Clinical Features of CHEDIAK-HIGASHI Syndrome
Railroad (microtubules) are out --\> IMPAIRED PHAGOLYSOSOME formation; INCREASED PYOGENIC INFECTIONS (can't destroy consumed organisms), NEUTROPENIA, GIANT GRANULES in LEUKOCYTES (accumulation), Defective PRIMARY HEMOSTASIS (abn dense granules in platelets), ALBINISM (can't transport melanin), PERIPHERAL NEUROPATHY (can't pass nutients over long distances to end of nerves)
50
Most Effective Destruction of Phagocytosed material
O2 dependent killing is most effective - HOCl\* generated by oxidative burst in phagolysosomes
51
O2 INDEPENDENT Destruction of Phagocytosed material
Lysozyme in macrophages and major basic protein in eosinophils
52
What enzyme converts O2 --\> O2\*-
NADPH oxidase
53
What enzyme conversts O2\*- --\> H2O2
SUPEROXIDE DISMUTASE (SOD)
54
What enzyme converts H2O2 --\> HOCl\*
MYELOPEROXIDASE (MPO)
55
CHRONIC GRANULOMATOUS DISEASE (CGD)
Poor O2-dependent killing due to NADPH OXIDASE DEFECT - can't make HOCl\*--\> recurrent infection and granuloma formation with CATALASE + organisms in particular STAPH AUREUS and PSEUDOMONAS CEPACIA; also Serratia marcescens, Nocardia and Aspergillus
56
Pts with CHRONIC GRANULOMATOUS DISEASE are SUSCEPTIBLE to which ORGANISMS?
CATALASE + STAPH AUREUS & PSEUDOMONAS CEPACIA; also Serratia marcescens, Nocardia and Aspergillus
57
Role of CATALASE in bacterial organisms
Destorys H2O2 and thus prevents HOCl\* formation and prevents O2 dependent killing
58
NITROBLUE TETRAZOLIUM test
Used to screen for CHRONIC GRANULOMATOUS DISEASE (NADPH oxidase deficiency); if leukocytes contain NADPH oxidase they will turn blue but they will remain clear if they do not contain NADPH oxidase
59
MYELOPEROXIDASE Deficiency
Cannot convert convert H2O2 --\> HOCl\*; Increased risk for CANDIDA infections; most pts Asx, Nitroblue Tetrazolium test is normal
60
Pts with MYELOPEROXIDASE Deficiency are susceptible to
CANDIDA infections
61
At end of acute inflammation, when and where do neutrophils undergo apoptosis?
Undergo apoptosis and disappear in the infected tissue within 24 hours of resolution
62
In acute inflammation, when do NEUTROPHILS reach peak levels?
~24 hours
63
In acute inflammation, when do MACROPHAGES reach peak levels?
2-3 days after inflammation begins
64
MACROPHAGES role in ACUTE INFLAMMATION
Ingest organisms via phagocytosis (augmented by opsonins) and destroy the phagocytosed material using enzymes (lysozyme) in secondary granules (O2 independent killing); they also MANAGE THE NEXT STEP of inflammation - proceed to Resolution/healing, further acute inflamm, abscess formation or chronic inflamm
65
ANTI-INFLAMMATORY CYTOKINES produced by MACROPHAGES to induce resolution and healing
IL-10 and TGF-β
66
CYTOKINE produced by MACROPHAGES to CONTINUE ACUTE INFLAMMATION
IL-8 recruits ADDITIONAL NEUTROPHILS; marked by PERSISTENT PUS formation
67
Role of MACROPHAGES in ABSCESS formation
Mediate FIBROSIS via FIBROGENIC GROWTH FACTORS and cytokines
68
Role of MACROPHAGES in CHRONIC INFLAMMATION
Present Ag to active CD4+ helper T cells which promote cyokines --\> chronic inflamm
69
CD4+ HELPER T CELL ACTIVATION
EXTRACELLULAR Ag is phagocytosed & presented on MHC Class II by APCs (dendritic cells or macrophages); 2nd signal B7 on APC binds to CD28 on CD4+ helper T cellEXTRACELLULAR Ag is phagocytosed & presented on MHC Class II by APCs (dendritic cells or macrophages); 2nd signal B7 on APC binds to CD28 on CD4+ helper T cellEXTRACELLULAR Ag is phagocytosed & presented on MHC Class II by APCs (dendritic cells or macrophages); 2nd signal B7 on APC binds to CD28 on CD4+ helper T cellEXTRACELLULAR Ag is phagocytosed & presented on MHC Class II by APCs (dendritic cells or macrophages); 2nd signal B7 on APC binds to CD28 on CD4+ helper T cellEXTRACELLULAR Ag is phagocytosed & presented on MHC Class II by APCs (dendritic cells or macrophages); 2nd signal B7 on APC binds to CD28 on CD4+ helper T cellEXTRACELLULAR Ag is phagocytosed & presented on MHC Class II by APCs (dendritic cells or macrophages); 2nd signal B7 on APC binds to CD28 on CD4+ helper T cell
70
TH1 cells secrete:
IL-2 and IFN-γ
71
TH2 cells secrete:
IL-4, IL-5, and IL-10
72
Function of IL-2
T cell growth factor and CD8+ T cell activator
73
Function of IFN-γ
Activates macrophages; in granuloma formation it converts macrophages to EPITHELIOID HISTIOCYTES & GIANT CELLS
74
Function of IL-4
Facilitates B-cell class switching to IgG and IgE
75
Function of IL-5
Eosinophil chemotaxis and activation, maturation of B cells to plasma cells, and class switching to IgA
76
Function of IL-10
Inhibits TH1 phenotype; also produced by macrophages if they decide its time for resolution prior to chronic inflamm
77
CD8+ CYTOTOXIC T CELL ACTIVATION
INTRACELLULAR Ag is processed and presented on MHC Class I (expressed by all nucleated cells and platelets); 2nd signal IL-2 from CD4+ TH1 cellsINTRACELLULAR Ag is processed and presented on MHC Class I (expressed by all nucleated cells and platelets); 2nd signal IL-2 from CD4+ TH1 cellsINTRACELLULAR Ag is processed and presented on MHC Class I (expressed by all nucleated cells and platelets); 2nd signal IL-2 from CD4+ TH1 cellsINTRACELLULAR Ag is processed and presented on MHC Class I (expressed by all nucleated cells and platelets); 2nd signal IL-2 from CD4+ TH1 cellsINTRACELLULAR Ag is processed and presented on MHC Class I (expressed by all nucleated cells and platelets); 2nd signal IL-2 from CD4+ TH1 cellsINTRACELLULAR Ag is processed and presented on MHC Class I (expressed by all nucleated cells and platelets); 2nd signal IL-2 from CD4+ TH1 cells
78
Immunoglobulins expressed by NAÏVE B CELLS
IgM and IgD
79
B CELL ACTIVATION --\> IgM or IgD Plasma Cell
Ag binds to surface IgM or IgD on NAÏVE B cell --\> maturation to IgM or IgD secreting plasma cell
80
B CELL ACTIVATION --\> IgA, IgG and IgE Secreting Plasma Cells
B cell Ag presentation to CD4+ Helper T cells via MHC Class II; 2nd signal comes from CD40 RECEPTOR ON B CELL binding to CD40L on HELPER T CELL -- Helper T cell secretes IL-4 (IgG and IgE class switching) and IL-5 (IgA class switching)B cell Ag presentation to CD4+ Helper T cells via MHC Class II; 2nd signal comes from CD40 RECEPTOR ON B CELL binding to CD40L on HELPER T CELL -- Helper T cell secretes IL-4 (IgG and IgE class switching) and IL-5 (IgA class switching)B cell Ag presentation to CD4+ Helper T cells via MHC Class II; 2nd signal comes from CD40 RECEPTOR ON B CELL binding to CD40L on HELPER T CELL -- Helper T cell secretes IL-4 (IgG and IgE class switching) and IL-5 (IgA class switching)B cell Ag presentation to CD4+ Helper T cells via MHC Class II; 2nd signal comes from CD40 RECEPTOR ON B CELL binding to CD40L on HELPER T CELL -- Helper T cell secretes IL-4 (IgG and IgE class switching) and IL-5 (IgA class switching)B cell Ag presentation to CD4+ Helper T cells via MHC Class II; 2nd signal comes from CD40 RECEPTOR ON B CELL binding to CD40L on HELPER T CELL -- Helper T cell secretes IL-4 (IgG and IgE class switching) and IL-5 (IgA class switching)B cell Ag presentation to CD4+ Helper T cells via MHC Class II; 2nd signal comes from CD40 RECEPTOR ON B CELL binding to CD40L on HELPER T CELL -- Helper T cell secretes IL-4 (IgG and IgE class switching) and IL-5 (IgA class switching)
81
DEFINING CHARACTERISTIC of GRANULOMATOUS INFLAMMATION
EPITHELIOID HISTIOCYTES surrounded by GIANT CELLS and a rim of LYMPHOCYTES
82
Difference between NONCASEATING and CASEATING Granulomas
Noncaseating LACK central necrosis
83
Reaction to foreign material - noncaseating vs caseating granuloma
NONCASEATING granuloma
84
Histo hallmark of SARCOIDOSIS
Multiple NONCASEATING granulomas in several tissues, in particular the LUNG
85
Histo hallmark of BERYLLIUM EXPOSURE
NONCASEATING granuloma in the LUNG
86
Histo hallmark of CROHN DISEASE
NONCASEATING granuloma
87
Histo hallmark of ULCERATIVE COLLITIS
CRYPT ABSCESSES
88
Organisms that display CASEATING GRANULOMAS
TB and Fungal infections
89
Stains for CASEATING GRANULOMAS
AFB stain to look for TB and a GMS (Silver) stain to look for FUNGAL INFECTIONS
90
Histo hallmark of CAT SCRATCH DISEASE
STELLATE SHAPED NONCASEATING granuloma
91
Process of GRANULOMA FORMATION (both caseating and noncaseating)
MACROPHAGES process and present Ag via MHC Class II to CD4+ HELPER T CELLS --\> MACROPHAGES SECRETE IL-12 inducing CD4+ helper T cells to differentiate to TH1 subtype --\> TH1 cells secrete IFN-γ which converts macrophages to epithelioid histiocytes and giant cellsMACROPHAGES process and present Ag via MHC Class II to CD4+ HELPER T CELLS --\> MACROPHAGES SECRETE IL-12 inducing CD4+ helper T cells to differentiate to TH1 subtype --\> TH1 cells secrete IFN-γ which converts macrophages to epithelioid histiocytes and giant cellsMACROPHAGES process and present Ag via MHC Class II to CD4+ HELPER T CELLS --\> MACROPHAGES SECRETE IL-12 inducing CD4+ helper T cells to differentiate to TH1 subtype --\> TH1 cells secrete IFN-γ which converts macrophages to epithelioid histiocytes and giant cellsMACROPHAGES process and present Ag via MHC Class II to CD4+ HELPER T CELLS --\> MACROPHAGES SECRETE IL-12 inducing CD4+ helper T cells to differentiate to TH1 subtype --\> TH1 cells secrete IFN-γ which converts macrophages to epithelioid histiocytes and giant cellsMACROPHAGES process and present Ag via MHC Class II to CD4+ HELPER T CELLS --\> MACROPHAGES SECRETE IL-12 inducing CD4+ helper T cells to differentiate to TH1 subtype --\> TH1 cells secrete IFN-γ which converts macrophages to epithelioid histiocytes and giant cells
92
Function of IL-12 in Granuloma Formation
Induce CD4+ helper T cells to become TH1 subtype
93
DIGEORGE SYNDROME
Devo failure of 3rd and 4th PHARYNGEAL POUCHES due to 22q11 microdeletion --\> T-cell deficiency (lack of thymus), HYPOCALCEMIA (lack of parathyroids), abnormalities of the heart, great vessels and face
94
Severe Combined Immunodeficiency Disorder (SCID)
Defective cell-mediated and humoral immunity (defective T and B cell immunity)
95
Pts with SCID are Susceptible to:
No T cells --\> Fungal and viral No B cells --\> bacteria and protozoa
96
Tx for SCID
Isolation (bubble boy) and stem cell transplant (hematopoietic stem cells)
97
X-Linked AGAMMAGLOBULINEMIA
LACK OF IMMUNOGLOBULIN due to disordered B cell maturation; MUTATED BRUTON TYROSINE KINASE (BTK)
98
INFECTIONS found in X-Linked AGAMMAGLOBULINEMIA patients
BACTERIA (no IgG to opsonize), ENTEROVIRUS and GIARDIA (no IgA to protect mucosa); also avoid live vaccines
99
COMMON VARIABLE IMMUNODEFICIENCY (CVID)
Low Ig due to B cell or helper T cell defect
100
Pts with Common Variable Immunodeficiency are susceptible to:
Susceptible to BACTERIA, ENTEROVIRUSES and GIARDIA LAMBILIA; also increased risk for AUTOIMMUNE DISEASES and LYMPHOMA
101
MC Ig Deficiency
IgA --\> mucosal infection (esp viral)
102
IMMUNOGLOBULIN DEFICIENCY assoc with CELIAC DISEASE
IgA
103
HYPER-IgM SYNDROME
MUTATED CD40L (on helper T cells) or MUTATED CD40 RECEPTOR on B cells --\> no second signal is delivered --\> CYTOKINES necessary for class switching NOT PRODUCED --\> LOW IgA, IgG, IgE --\> RECURRENT pyogenic infections (poor opsonization - low IgG), esp at mucosal surfaces (low IgA)
104
WISKOTT-ALDRICH SYNDROME
Triad - Thrombocytopenia, Eczema, and recurrent infections
105
Pts with C5-9 DEFICIENCY are susceptible to
NEISSERIA infection (N gonorrhoeae and N meningitidis)
106
Clinical Features of C1 INHIBITOR DEFICIENCY
PERIORBITAL EDEMA and muscoal surfaces (over activation of complement --\> increased vasodilation and increased vascular permeability --\> edema)
107
Type of Hypersensitivity Reaction in SLE
Type II (cytotoxic) and Type III - Ab aginst host damage multiple tissues
108
Clinical Features of SLE
Malar butterfly rash, arthritis, pleuritis and pericarditis, CNS psychosis, RENAL DAMAGE, Endocarditis, myocarditis, or pericarditis, ANEMIA, THROMBOCYTOPENIA, or LEUKEMIA
109
MC RENAL injury in SLE
Diffuse Proliferative GlomerulonephrITIS
110
Classic ENDOCARDITIS injury in SLE
LIBMAN-SACKS endocarditis - small sterile deposits on BOTH sides of the mitral valve
111
HEMATOLOGIC findings in SLE
PANCYTOPENIA - due to auto-Ab against cell surface proteins
112
MC cause of death in SLE
Renal failure and infection
113
Abs used for screening and Dx in SLE
Screen with ANA - sensitive but not specific; Dx made with anti-dsDNA Abs - highly specificScreen with ANA - sensitive but not specific; Dx made with anti-dsDNA Abs - highly specificScreen with ANA - sensitive but not specific; Dx made with anti-dsDNA Abs - highly specific
114
DRUG-INDUCED SLE - Abs and common causes
AntihiSTONED Ab; Causes are HIP - Hydralazine, Isoniazid, Procainamide
115
SJOGREN SYNDROME Pathophys and Hypersensitivity Rxn
Autoimmune destruction of LACRIMAL and SALIVARY glands; lymphocyte-mediated damage - Type IV
116
Clinical Features of SJOGREN SYNDROME
"Can't chew a cracker with this damn dirt in my eyes" - DRY EYES (keratoconjunctivitis), DRY MOUTH (xerostomia) and recurrent DENTAL CARRIES in older woman (50-60yo)
117
Abs found in SJOGREN SYNDROME
ANA (screening) and ANTI-RIBONUCLEOPROTEIN (anti-SS-A/Ro and anti-SS-B/La)
118
Higher risk COMPLICATION of SJOGREN SYNDROME and its presentation:
B-cell (marginal zone) lymphoma presenting as UNILATERAL enlargement of PAROTID GLAND late in disease course
119
Abs in SCLERODERMA
ANA and ANTI-DNA TOPOISOMERASE I (Scl-70)
120
CREST SYNDROME and its Abs
Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasias of the skin; ANTI-CENTROMERE (CRESTomere)
121
Abs in MIXED CONNECTIVE TISSUE DISEASE
Abs against U1 RIBONUCLEOPROTEIN
122
LABILE tissues
tissues that possess STEM CELLS that continuously cylce to regenerate tissue
123
Examples of LABILE tissues and LOCATION OF STEM CELLS
Small and large bowel - SCs in MUCOSAL CRYPTS; Skin - SCs in BASAL LAYER; Bone marrow - hematopoietic SCs
124
MARKER of HEMATOPOIETIC STEM CELLS
CD34
125
STEM CELL of the LUNG
Type II Pneumocytes
126
STABLE tissues
Comprised of cells that are QUIESCENT (G0) but can reenter the cell cycle to REGENERATE TISSUE WHEN NECESSARY
127
Examples of STABLE TISSUES
Regeneration of LIVER by compensatory hyperplasia after partial resection; PROXIMAL RENAL TUBULE shows regeneration during acute tubular necrosis
128
PERMANENT tissues
LACK significant regenerative potential so they undergo repair (fibrous scar)
129
Examples of PERMANENT TISSUES
Myocardium, skeletal muscle and neurons
130
Initial phase of Repair in wound healing
Granulation Tissue
131
Granulation Tissue in Wound Healing consists of:
FIBROBLASTS (TYPE III COLLAGEN), capillaries, and myofibroblasts (CONTRACT wound)
132
COLLAGEN CHANGE in SCAR formation
Type III is REPLACED BY TYPE I COLLAGEN
133
COLLAGENASE in Scar formation
REMOVES TYPE III COLLAGEN and REQUIRES Zn as a cofactor
134
COLLAGENASE requires which COFACTOR
ZINC
135
TYPE I Collagen CHARACTERISTICS and LOCATION
High tensile strength - present in skin bONE, tendons and most organs
136
Type II Collagen LOCATION
carTWOlage
137
TYPE III Collagen CHARACTERISTICS and LOCATION
Pliable - found in BVs, granulation tissue and embryonic tissue
138
TYPE IV Collagen LOCATION
Basement Membrane
139
Role of TGF-α in Tissue Regeneration and Repair
EPITHELIAL and FIBROBLAST Growth Factor
140
Role of TGF-β in Tissue Regneration and Repair
FIBROBLAST GROWTH FACTOR and INHIBITS INFLAMMATION
141
Role of PLATELET-DERIVED GROWTH FACTOR in Tissue Regeneration and Repair
GF for endothelium, smooth muslce and fibroblasts
142
Role of FIBROBLAST GROWTH FACTOR in Tissue Regeneration and Repair
ANGIOGENESIS and MEDIATES SKELETAL DEVELOPMENT
143
Role of VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) in Tissue Regeneration and Repair
ANGIOGENESIS
144
GROWTH FACTORS important in ANGIOGENESIS in Tissue Regeneration and Repair
VEGF and FGF
145
Role of MYOFIBROBLASTS in Secondary intention wound healing
Edges are not approximated and granulation tissue fills the defect - MYOFIBROBLASTS THEN CONTRACT THE WOUND forming a scar
146
Conditions leading to DELAYED WOUND HEALING
INFECTION (MC is S. aureus), VITAMIN C DEFICIENCY, COPPER DEFICIENCY, OR ZINC DEFICIENCY
147
VITAMIN C DEFICIENCY in Wound healing
Vit C is impt cofactor in HYDROXYLATION OF PROLINE AND LYSINE PROCOLLAGEN RESIDUES which is necessary for eventual cross-linking
148
COPPER DEFICIENCY in Wound healing
COPPER is a cofactor for LYSYL OXIDASE which CROSS-LINKS LYSINE and HYDROXYLYSINE TO FORM STABLE COLLAGEN
149
Type of Collagen in HYPERTROPHIC SCAR
TYPE I
150
KELOID - Pathophys, genetics and location
Excess production of scar tissue (TYPE III COLLAGEN) that is out of proportion to the wound; AFRICAN AMERICANS more common; affects EARLOBES, FACE and UPPER EXTREMITIES
