What is ulcerative inflammation?
- A local defect, or excavation, of the surface of an organ or tissue
- Produced by the shedding of inflamed necrotic tissue
- Commonly found in mouth, stomach, GU, intestines
- Also common in skin and subcutaneous tissue of lower extremities due to ischemia
What are the three outcomes of inflammation?
1) Resolution - clearance of injury and replacement of cells leading to normal function
2) Repair - healing by fibrosis, collagen deposition, and granulation tissue leading to loss of function
3) Chronic inflammation - angiogenesis, fibrosis, progressive tissue injury
What is chronic inflammation?
- Not simply persisting acute inflammation
- Concurrent repair, tissue disruption and inflammation
- Can result from persistent injurious stimulus or a dysregulated adaptive immune system
What is chronic pyelonephritis?
- Chronic relapsing inflammation of renal tissue
- Usually caused by relapsing ascending UTIs
- Dilation of ureter
- Atrophy of cortex
In chronic inflammation, _____ migrate to tissue sites from the blood.
Monocytes
Macrophages are activated by…
- Bacterial toxins
- T-cells products, especially INF-γ
What is the role of IFN-γ in chronic inflammation?
- Attracts and recruits more monocytes/macrophages
- At unusually high levels, can result in granulomatous inflammation
What is granulomatous inflammation?
- A type of chronic inflammation
- Results from a difficult to eliminate stimulus
- Lump of cells forms that walls the stimulus off from the rest of the tissue
- Classic example is TB, where persistent bacteria causes prolonged IFN-γ production
- May also result from an inert material that is too big to be phagocytosed
What are caseating granulomas?
- Granulomas that have a central necrosis surrounded by a rim of macrophages and lymphocytes
- Resembles cheese
- Typically a feature of TB
What is necrosis?
- Unregulated form of cell death resulting from damage to cell membranes and leakage of cellular contents
- Causes inflammation
- Results from denaturation of intracellular proteins, loss of cell membrane integrity, and enzymatic digestion of lethally injured cells
- Always pathological
How is immune dysregulation implicated in IBD?
- A barrier defect in the epithelia results in antigen and foreign substance entry into the mucosa
- Hyperreactive immune cells, dysregulated cytokine secretion can result in chronic intestinal inflammation
- Can lead to increased risk of colorectal cancer
What is IBD?
- Chronic inflammation of the digestive tract
- Ulcerative colitis - predominantly affects the colon
- Crohn’s disease - can affect any part of the GI tract and often involves granuloma formation
What is an epitheloid cell?
lMacrophages that have turned into epitheloid cells which resemble epithelial cells but act as “filler” cells
What is the colliquative pattern of necrosis?
- Dead tissue appears semi-liquid
- Often seen in pyogenic infection (abscess)
- Typical form of necrosis seen in the brain
What is the coagulative pattern of necrosis?
- Cellular outlines and tissue architecture is preserved
- Often seen in ischemic necrosis of tissues (ex. MI)
What are the steps of neutrophil extravasation?
- Inflammatory mediators such as histamine are released and increases endothelial permeability
- Activated endothelial cells display integrins that snag at neutrophils
- Extravasation of neutrophils into the tissue occurs via rolling adhesion and diapedesis
- Host proteins (complement C5a) and antigen proteins attract neutrophils via chemotaxis
- Neutrophils begin to phagocytose bacteria and debris
Steroids inhibit the _____ step of the arachidonic acid pathway.
Phospholipase
What is supparative inflammation?
- Inflammation resulting in the production of pus (also called purulent)
- Characterisitc of infection with pyogenic bacteria, such as staphylococci
- Can lead to abscesses, with are large, localized, enclosed collections of pus
- Pus is thick, yellowish or greenish fluid consisting of bacteria and dead neutrophils, with tissue debris and serum
What are hallmarks of chronic inflammation?
- Infiltration on non-neutrophil WBCs (macrophages and lymphocytes)
- Arhcitectural destruction of tissue
- Healing by fibrosis
How do transudates differ from exudates?
Transudates: more watery, not due to inflammation, have low protein count (ex. HF, liver disease)
Exudates: higher protein count, occur due to inflammation/infection
What are the most important chemical mediators of inflammation?
Plasma-derived: complement proteins
Preformed: histamine
Newly-synthesized: nitric oxide, cytokines, arachidonic acid metabolites
Which arachidonic acid metabolite is responsible for pain in inflammation?
Prostaglandins, which are produced from cyclooxegenase
What is serous inflammation?
- Results from a minor injury
- Will result in thin fluid, with not a lot of neutrophils (blister, virus, burn)
- Fluid is derived from the plasma or mesothelia (effusion)
What is fibrinous inflammation?
- Characterized by fibrin deposition
- Occurs in marked vascular permeability
- More extensive leakage of fluid allows for passage of large plasma proteins (fibrinogen) into the tissue
- Forms exudate
- Seen in acute pericarditis
