Inflammation and Tissue Repair Flashcards
What are the 5 signs of an infection?
Heat, Redness, Swelling, Pain, Loss of Function
What is the primary cellular type in acute inflammation?
Neutrophils
What are the primary cells present during chronic inflammation?
Macrophages and Lymphocytes
What are the most common cells that recognize a stimuli of initiation of inflammation?
Epithelial Cells
Dendritic Cells
Phagocytes
How do they recognize the stimulus and what do they do?
Toll-Like Receptors (extracellular) - initiates secretion of TNF, adhesions
Inflammasome (intracellular) - activates caspase and secretes IL-1
How does vascularity change and what is responsible for the change?
Vasodilation in the area by NO and Histamine
Then increased permeability - Bradykinin and Histamine
+Increased lymph flow
If a patient has chronic hepatic stenosis causing a build up of fluid in the abdomen, what kind of fluid is it?
Transudate - fluid with minimal protein caused by decreased venous flow. Specific gravity below 1.012
If a patient is suffering from CHF causing increasing shortness of breath, what kind of fluid?
Transudate, bluid up of fluid in the interstitial due to decreased osmotic pressure. Can be caused by lack of protein/albumin as well.
What kind of fluid is present after an acute inflammation response?
Exudate fluid. Specific gravity above 1.020
Caused by an increase in endothelial cell permeabilty during the inflammatory response.
What cytokines are responsible for upregulating adhesions (selectins and integrins) on the vascular wall and leukocyte surface?
IL-1 and TNF, released from Macrophages
What is diapedesis?
The process of migrating between the endothelium via CD31 or PECAM-1 present on the endothelial wall and on the surface of leukocytes making a stable bond.
How do the leukocytes know where the injury is located after they migrate through the endothelial?
Chemokine concentration gradient leads them to the area of inflammation.
- chemokines
- complement
- leukotrienes
What occurs after the lymphocyte reaches the site of inflammation? How does it activate?
Recognizes the target that is opsoninized, binds to a receptor on the leukocyte, undergoes phagocytosis and respiratory burst/ROS to degrade target.
What protein is most important for leukocytes’ respiratory burst ability?
iNOS P450 to create the ROS used degrade and kill the engulfed target
What cytokine is responsible for causing pain, or lowering the threshold for pain at the inflammation site?
Bradykinin
What kind of inflammation is most common for CHF exacerbation and burns?
Serous Inflammation, most mild inflammation, limited protein involvement in the leaky endothelium
Which type of inflammation is primarily involved with linings in the body?
Fibrinous Inflammation. Chronic leaking endothelium that becomes converted to fibrin.
ie. Fibrinous Pericarditis, Rheumatic Fever, Fibrinous Pleuritis
- -Usually contributed with uremia and kidney insufficiency
What kind of inflammation are abscesses and organ inflammation? (ie appendicitis)
Suppurative Inflammation. Large number of neurophils in a central area surrounded by inflammation. Most common form.
What kind of inflammation do people with diabetes get on their lower extremities due to poor circulation?
Ulceration Inflammation, superficial tissue or covering of an organ
How is chronic inflammation different than acute inflammation?
Prolonged inflammation, weeks to years. Persistant infections or exposure, and autoimmune disorders.
–Monocytes/Macrophages are most common type of cell present secreting cytokines (IFN-gamma) chronically activating the T-cells.
What is the specific type of cell called involved in Granulomatous Inflammation?
Epithelioid Histiocytes (Macrophages), IFN-gamma induces the Histiocytes to fuse together into Multinucleated Giant Cell
What are common causes of granulomatous inflammation?
- Foreign Body
- Infections
- Self - Reactions
- Syphilis
What two cytokines contribute to fever?
Pyrogens (bacterial products)
IL-1
TNF
PGE2 - secondary messenger in hypothalamus
What are some acute phase proteins, how are they stimulated, and how are they measured?
IL-6 stimulates production in the liver.
Various acute phase proteins include: C-reactive protein, Fibrinogen, Amyloid A
Fibrinogen can be measured sedimentation rate to see if there is any acute inflammation
What type of leukocytosis is involved in bacterial infections?
Neutraphilia, “Left Shift” when immature leukocytes are released from bone marrow during bacterial infections.
What kind of Leukocytosis is involved in viral infections?
Lymphocytosis
What kind of cells are most commonly the cause of seasonal allergies?
Eosinophils
What components are involved in regeneration?
- remnants of injury
- endothelial cells
- fibroblasts
What are the different kinds of stem cells used to regenerate tissues?
Embryonic - all tissue possibilities
Adult stem cells - lineage specific
Multipotent Progenitor cells - bone marrow multiple possibilities
How does injured tissue know to regenerate?
Leukocytes, Parenchymal, and Stroma cells release growth factors binding to receptors causing upregulation of gene expression in the area stimulating proliferation, size, and survival.
What growth factors are involved with angiogenesis?
VEGF and FGF
What growth factor comes from a multitude of cell types that stimulates angiogenesis and migration of fibroblasts?
Fibroblast Growth Factor - FGF
Which growth factors stimulate production of the ECM?
Platelet derived growth factors and Transforming growth factor B. (PDGF and TGF-B)
Specifically what growth factor suppresses proliferation of endothelial cells and migration?
Transforming Growth Factor B
What are the two parts of ECM and roles?
Interstitial Matrix and the Basement membrane
- mechanical support
- scaffold essential for healing w/o scarring
What are some of the structural components of the ECM?
Collagen & Elastin/Fibrillin
- Proteoglycans/Hyaluronan
- Fibronectin
- Laminin
- Adhesions
What condition is consistant with being hyperextensive, rupture of vessels and organs, and poor wound healing?
Ehler-Danlos Syndrome, classically deficiency in production of collagen type V
What condition has defective Fibrillin and what are the consequences?
Marfan Syndrome, long extremities/fingers, aortic dissection, dislocated eye lens, and abnormal valves.
When and where is connective tissue used to heal injuries?
When the injury is severe/chronic with destruction of the stroma and if they involve non-dividing cells.
What specialized tissue is typical of a healing wound that is only present for 3-5 days?
Granulation Tissue
What are the steps in repairing an injury?
- Angiogenesis
- Fibroblast migration/proliferation
- Extracellular matrix deposition
- Maturation and Fibrous Tissue
What are the key growth factors involved in angiogenesis of ischemic tissue?
VEGF and NO
+ FGF
Which growth factors are involved in fibroblast migration and depositing of ECM?
TGF-B
PDGF
FGF
What protein is central in maturation of scar tissue?
Matrix Matalloprotein contraining zinc (MMP)
At what point is there wound contraction and remodeling?
3 days to 3 months+
What kind of wounds most likely heal using primary intention?
Wounds that are linear, non-infected, and well approximated. Typically heal without a scar.
How are wounds that heal with secondary intention?
More significant wounds and more damage, large amount of granulation tissue and inflammation.
Is the skin ever as strong as it was prior to the injury?
No. ~10% strength after 1 week and after sutures removed
Even by 3 months strength is only 70-80%
What factors can decrease healing?
DM, Steriods, infections, poor circulation, tension on the wound, and FBs present in the wound
What type of scar formation is typical of African Americans and is inherited?
Keloid formation, where there is excess collagen and raised scar. Exuberant granulation tissue
