CH2 - Inflammation, Inflammatory Disorders, and Wound Healing Flashcards
What does inflammation allow?
Allows inflammatory cells, plasma proteins (e.g., complement), and fluid to exit blood vessels and enter the interstitial space
Inflammation is divided into what?
Divided into acute and chronic inflammation
What is inflammation characterized by?
the presence of edema and neutrophils in tissue
Inflammation arises in response to what?
infection (to eliminate pathogen) or tissue necrosis (to clear necrotic debris)
innate immunity
Immediate response with limited specificity
What are the mediators of acute inflammation?
Toll-like receptors, Arachidonic acid (AA) metabolites, Mast cells, Complement, Hageman Factor
Toll-like receptors
Present on cells of the innate immune system (e.g., macrophages and dendritic cells)
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
TLR activation results in what?
upregulation of NF-kB, a nuclear transcription factor
What does NF-kB do?
activates immune response genes leading to production of multiple immune mediators
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.
Arachidonic acid (AA) metabolites
- AA is released from the phospholipid cell membrane by phospholipase A2 and then acted upon by cyclooxygenase or 5-lipoxygenase.
Cyclooxygenase
produces prostaglandins (PG) a. PGI2, PGD2 and PGE2 mediate vasodilation and increased vascular permeability. PGE2 also mediates pain.
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.
Where are Mast cells located?
- Widely distributed throughout connective tissue
How are Mast cells activated?
(1) tissue trauma (2) complement proteins C3a and C5a (3) cross-linking of cell-surface IgE by antigen
Mast cells immediate response is?
involves the release of preformed histamine granules, which mediate vasodilation of arterioles and increased vascular permeability
Mast cells delayed response is?
involves production of arachidonic acid metabolites, particularly leukotrienes.
Complement
proinflammatory serum proteins that complement inflammation
Where is complement located?
Circulate as inactive precursors;
Activation of complement occurs via what?
Classical pathway, Alternative pathway, MBL pathway
Classical pathway
C1 binds IgG or IgM that is bound to antigen
Alternative pathway
Microbial products directly activate complement.
Mannose binding lectin pathway
mannose binding lectin (MBL) pathway MBL binds to mannose on microorganisms and activates complement
All pathways of complement result in?
production of C3 convertase (mediates C3?>C3a and C3b, producing C5 convertase (mediates C5?>C5a and C5b)
What forms the MAC?
C5b complexes with C6-C9 to form the membrane attack complex (MAC)
C3a and C5a
(anaphylatoxins)?trigger mast cell degranulation, resulting in histamine-mediated vasodilation and increased vascular permeability
C5a
chemotactic for neutrophils
C5b
opsonin for phagocytosis
MAC
Lyses microbes by creating a hole in the cell membrane
Where is Hageman factor (Factor XII) produced?
Inactive proinflammatory protein produced in liver
How is Hageman factor (Factor XII)?
Activated upon exposure to subendothelial or tissue collagen;
Hageman factor (Factor XII) activates what?
- Coagulation and fibrinolytic systems 2. Complement 3. Kinin system
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.
What are the cardinal signs of inflammation?
Redness (rubor) and warmth (calor), swelling, pain, fever
What is Redness (rubor) and warmth (calor) due to?
- Due to vasodilation, which results in increased blood flow
How does Redness (rubor) and warmth (calor) occur?
Occurs via relaxation of arteriolar smooth muscle;
Key mediators of Redness (rubor) and warmth (calor) are?
histamine, prostaglandins, and bradykinin
Swelling (tumor) is due to what?
Due to the leakage of fluid from postcapillary venules into the interstitial space (exudate)
What are the Key mediators of swelling?
(1) histamine, which causes endothelial cell contraction and (2) tissue damage, resulting in endothelial cell disruption,
Pain (dolor)
Bradvkinin and PGE2 sensitize sensory nerve endings.
Fever
- 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.
What are the steps in neutrophil arrival?
Margination, Rolling, Adhesion, Transmigration and Chemotaxis, Phagocytosis, Destruction of phagocytosed material, resolution
Step 1?Marginatum
- Vasodilation slows blood flow in postcapillary venules. 2. Cells marginate from center of flow to the periphery.
Step 2?Rolling
- 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
P-selectin is released from where and what does it mediate?
release from Weibel Palade bodies, is mediated by histamine.
E-selectin is induced by what?
TNF and IL-1.
Step 3?Adhesion
- 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
Leukocyte adhesion deficiency
is most commonly due to an autosomal recessive defect of integrins (CD18 subunit)
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.
Step 4?Transmigration and Chemotaxis
- Leukocytes transmigrate across the endothelium of postcapillary venules and move toward chemical attractants (chemotaxis).
Neutrophils are attracted by
bacterial products, IL-8, C5a, and LTB4
Step 5?Phagocytosis
- 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.
Chediak-Higashi syndrome
is a protein trafficking defect (autosomal recessive) characterized by impaired phagolysosome formation.
Clinical features of Chediak-Higashi syndrome include
Increased risk of pyogenic infections, Neutropenia, Giant granules in leukocytes, Defective primary hemostasia, Albinism, Peripheral neuropathy
Why is there Neutropenia in Chediak Higashi syndrome?
(due to intramedullary death of neutrophils)
In chediak higashi there are Giant granules in leukocytes because?
due to fusion of granules arising from the Golgi apparatus
In chediak higashi Defective primary hemostasia is due to?
abnormal dense granules in platelets
Step 6?Destruction of phagocytosed material
- O2-dependent killing is the most effective mechanism. 2. HOCl generated by oxidative burst in phagolysosomes destroys phagocytosed microbes.
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).
NADPH oxidase
O2 is converted to O2. by (oxidative burst).
SOD
O2. is converted to H202, by superoxide dismutase
MPO
H202 is converted to HOCl (bleach) by myeloperoxidase (MPO).
CGD is characterized by?
poor O2-dependent killing.
CGD is Due to?
NADPH oxidase defect (X-linked or autosomal recessive)
What does CGD lead to?
recurrent infection and granuloma formation with catalase-positive organisms, particularly Staphylococcus aureus, Pseudpmonas cepacia, Serratia marcescens, Nocardia, and Aspergillus
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.
MPO deficiency results in?
defective conversion of H202 to HOCl
MPO deficiency symptoms?
Increased risk for Candida infections; however, most patients are asymptomatic.
MPO deficiency and NBT?
normal; respiratory burst O2. to H2O2 is intact.
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).
Step 7?Resolution
Neutrophils undergo apoptosis and disappear within 24 hours after resolution of the inflammatory stimulus.
Macrophages
Macrophages predominate after neutrophils and peak 2-3 days after inflammation begins.
What are macrophages derived from?
monocytes in blood
How do macrophages arrive in tissue?
via the margination, rolling, adhesion, and transmigration sequence
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)
What are the outcomes for macrophages managing the next step of the inflammatory process?
Resolution and healing, 2. Continued acute inflammation, Abscess, Chronic inflammation
Macrophages induce Resolution and healing by?
Anti-inflammatory cytokines (1L-10 and TGF-(Beta) are produced by macrophages.
Macrophages induce Continued acute inflammation by?
persistent pus formation; IL-8 from macrophages recruits additional neutrophils.
Macrophages induce Abscess by?
acute inflammation surrounded by fibrosis; macrophages mediate fibrosis via fibrogenic growth factors and cytokines.
Macrophages induce chronic inflammation by?
Macrophages present antigen to activate CD4+ helper T cells, which secrete cytokines that promote chronic inflammation
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
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.
T lymphocytes are produced where?
Produced in bone marrow as progenitor T cells
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
T cells use TCR complex for?
(TCR and CD3) for antigen surveillance
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
Activation of T cells requires what?
(1) binding of antigen/MHC complex and (2) an additional 2nd signal.
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.
Activated CD4+ helper T cells do what?
secrete cytokines that help inflammation and are divided into two subsets.
What are the subsets of activated CD4+?
TH1 and TH2
TH1 subset
secretes IL-2 (T cell growth factor and CD8+ T cell activator) and IFN-gamma (macrophage activator)
TH2 subset
IL-4, IL-5, IL-10
TH2 subset secretes IL-4 which results in?
facilitates B-cell class switching to IgG and IgE
TH2 subset secretes IL-5 which results in?
eosinophil chemotaxis and activation, maturation of B cells to plasma cells, and class switching to IgA
TH2 subset secretes IL-10 which?
inhibits TH1 phenotype
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.
What provides the 2nd activation signal for CD8+?
IL-2 from CD4+ TH1 cell
Cytotoxic T cells are activated for?
killing
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
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.
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
What provides the 2nd activation signal
CD40 receptor on B cell binds CD40L on helper T cell
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)
What is granulomatous inflammation?
Subtype of chronic inflammation, Characterized by granuloma, which is a collection of epithelioid histiocytes
What are epithelioid histiocytes?
macrophages with abundant pink cytoplasm, usually surrounded by giant cells and a rim of lymphocytes
What is granulomatous inflammation divided into?
noncaseating and caseating subtypes
What is noncaseating granulomas?
lack central necrosis
Common etiologies for noncaseating granulomas?
include reaction to foreign material, sarcoidosis, beryllium exposure, Crohn disease, and cat scratch disease,
Caseating granulomas
exhibit central necrosis and are characteristic of tuberculosis and fungal infections
What are the seps involved in granuloma formation?
- 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.
What is DiGeorge Syndrome?
Developmental failure of the third and fourth pharyngeal pouches
What is DiGeorge Syndrome?
Due to 22qll microdeletion
What does DiGeorge Syndrome presents with?
T-cell deficiency (lack of thymus); hypocalcemia (lack of parathyroids); and abnormalities of heart, great vessels, and face
Severe combined immunodeficiency
defective cell-mediated and humoral immunity
What are the etiologies for SCID?
Cytokine receptor defects, Adenosine deaminase (ADA) deficiency, MHC class II deficiency
Cytokine receptor defects
Cytokine signaling is necessary for proliferation and maturation of B and T cells.
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
MHC class II deficiency
MHC class II is necessary for CD4+ helper T cell activation and cytokine production
SCID is characterized by?
susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines
SCID treatment is?
sterile isolation (‘bubble baby ) and stem cell transplantation.
What is X-Linked agammaglobulinemia?
Complete lack of immunoglobulin due to disordered B-cell maturation, naive B cells cannot mature to plasma cells.
What is X-Linked agammaglobulinemia due to?
mutated Bruton tyrosine kinase; X-linked
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.
What is the caveat associated with X-Linked agammaglobulinemia?
Live vaccines (e.g., polio) must be avoided.
What is common variable immunodeficiency?
Low immunoglobulin due to B-cell or helper T-cell defects
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
IgA deficiency
Low serum and mucosal IgA; most common immunoglobulin deficiency
IgA deficiency increases the risk for?
Increased risk for mucosal infection, especially viral; however, most patients are asymptomatic.
Hyper IgM syndrome
Characterized by elevated IgM, Due to mutated CD40L (on helper T cells) or CD40 receptor (on B cells)
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
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.
What is Wiscott Aldrich syndrome?
Characterized by thrombocytopenia, eczema, and recurrent infections {defective humoral and cellular immunity)
What is Wiscott Aldrich syndrome due to?
mutation in the WASP gene; X-linked
What are the Complement Deficiencies?
C5-C9 deficiencies, CI inhibitor deficiency
C5-C9 deficiencies
increased risk for Neisseria infection (Ngonorrhoeae and N meningitidis)
CI inhibitor deficiency
results in hereditary angioedema, which is characterized by edema of the skin (especially periorbital, Fig. 2.3) and mucosal surfaces
Autoimmune disorders are characterized by?
immune-mediated damage of tissues, 1% prevalence in the US, Involves loss of self-tolerance
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).
Autoimmune disease is more common in?
women; classically affects women of childbearing age
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).
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.
Systemic Lupus Erythematosus is more common in?
women, especially African American females
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.
Anemia, thrombocytopenia, or leukopenia in SLE is due to?
autoantibodies against cell surface proteins
Most common causes of death in SLE?
Renal failure and infection
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.
What is the most common clinical features of systemic Lupus Erythematosus?
Diffuse proliferative glomerulonephritis, though other patterns of injury also occur.
Systemic Lupus Erythematosus and anemia, thrombocytopenia, or leukopenia is due to?
autoantibodies against cell surface proteins
What are common causes of death for SLE?
renal failure and infection
SLE is characterized by
antinudear antibody ANA; sensitive, but not specific and anti dsDNA antibodies (highly specific)
Antihistone antibody is characteristic of?
drug-induced SLE.
What are some common causes of drug induced SLE?
- Hydralazine, procainamide, and isoniazid are common causes 2. Removal of drug usually results in remission.
30% of what cases are associated with SLE?
Antiphospholipid antibody syndrome
Antiphospholipid antibody syndrome is characterized by?
autoantibody against proteins bound to phospholipids. 2.
In antiphospholipid antibody syndrome what are the most common antibodies?
Anticardiolipin and lupus anticoagulant
In antiphospholipid antibody syndrome what tests are disrupted?
Leads to false-positive syphilis test and falsely-elevated PTT lab studies, respectively
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
What does antiphospholipid antibody syndrome require?
lifelong anticoagulation
What is sjogren syndrome?
Autoimmune destruction of lacrimal and salivary glands, lymphocyte-mediated damage (type IV hypersensitivity) with fibrosis
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
Sjogren syndrome is characterized by?
ANA and anti-ribonucleoprotein antibodies anti-SS-A/Ro and anti-SS-B/La)
Sjogren syndrome is often associated with?
other autoimmune diseases, especially rheumatoid arthritis
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
Scleroderma is
Autoimmune tissue damage with activation of fibroblasts and deposition of collagen (fibrosis)
Scleroderma is divided into?
diffuse and localized types
Diffuse type of scleroderma exhibits?
skin and early visceral involvement.
Scleroderma involves
Almost any organ can be involved; esophagus is commonly affected, resulting in disordered motility (dysphagia for solids and liquids).
Scleroderma is characterized by?
ANA and anti-DNA topoisomerase I (Scl-70) antibody
Scleroderma localized type exhibits?
local skin and late visceral involvement.
What is CREST syndrome?
For localized type scleroderma: Calcinosis/anti-Centroniere antibodies, Raynaud phenomenon. Esophageal dysmotility, Sclerodactyly, and Telangiectasias of the skin.
What is mixed connective tissue disease?
autoimmune-mediated tissue damage with mixed features of SLE, systemic sclerosis, and polymyositis
What is mixed connective tissue disease characterized by?
serum antibodies against U1 ribonucleoprotein
When is healing initiated?
when inflammation begins.
Wound healing occurs via?
a combination of regeneration and repair
In wound healing regeneration occurs via?
Replacement of damaged tissue with native tissue; dependent on regenerative capacity of tissue
Tissues are divided into three types based on?
regenerative capacity: labile, stable, and permanent.
Labile tissues
possess stem cells that continuously cycle to regenerate the tissue.
Examples of Labile tisues
- Small and large bowel (stem cells in mucosal crypts) 2. Skin (stem cells in basal layer) 3. Bone marrow (hematopoietic stem cells)
Stable tissues are
comprised of cells that are quiescent G0, but can reenter the cell cycle to regenerate tissue when necessary.
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.
Permanent tissues
lack significant regenerative potential (myocardium, skeletal muscle, and neurons).
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
Granulation tissue
Its formation is the initial phase of repair
In the initial phase of repair what does the fibroblasts do?
deposit type III collagen
In the initial phase of repair what does the capillaries do?
provide nutrients
Granulation tissue consists of?
fibroblasts (deposit type III collagen), capillaries (provide nutrients), and myofibroblasts (contract wound)
Granulation tissue eventually results in?
scar formation, in which type 111 collagen is replaced with type 1 collagen
Type III collagen is
pliable and present in granulation tissue, embryonic tissue, uterus, and keloids.
Type I collagen
has high tensile strength and is present in skin, bone, tendons, and most organs,
Collagenase
removes type 111 collagen and requires zinc as a cofactor.
Tissue regeneration and repair is mediated by?
paracrine signaling via growth factors (e.g macrophages secrete growth factors that target fibroblasts)
What results in gene expression and cellular growth?
Interaction of growth factors with receptors (e.g.. epidermal growth factor with growth factor receptor)
Examples of mediators of tissue repair and regeneration
TGF-alpha, TGF-beta, platelet, fibroblast growth factor, VEGF
TGF-alpha
epithelial and fibroblast growth factor
TGF-beta
important fibroblast growth factor; also inhibits inflammation
Platelet-derived growth factor
growth factor for endothelium, smooth muscle, and fibroblasts
Fibroblast growth factor
important for angiogenesis; also mediates skeletal development
Vascular endothelial growth factor (VEGF)
important for angiogenesis
Cutaneous healing occurs via
primary or secondary intention.
Primary intention
Wound edges are brought together (e.g., suturing of a surgical incision); leads to minimal scar formation
Secondary intention
Edges are not approximated. Granulation tissue fills the defect; myofibroblasts then contract the wound, forming a scar.
Delayed wound healing occurs in
- Infection (most common cause; S aureus is the most common offender)
Vitamin C is
an important cofactor in the hydroxylation of proline and lysine procollagen residues; hydroxylation is necessary for eventual collagen cross-linking.
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.
What is a cofactor for collagenase?
Zinc which replaces the type III collagen of granulation tissue with stronger type I collagen
What are some causes for delayed wound healing?
foreign body, ischemia, diabetes, and malnutrition,
Dehiscence is
rupture of a wound; most commonly seen after abdominal surgery
Hypertrophic scar is
excess production of scar tissue that is localized to the wound
Keloid is
excess production of scar tissue that is out of proportion to the wound
Keloid is characterized by
excess type III collagen
Keloid genetic predisposition
more common in African Americans
Keloid classically affects
earlobes, face, and upper extremities
