Pathoma Chapter 2D Flashcards
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
