Chronic Inflammation II Flashcards
(52 cards)
What is granulomatous inflammation?
Distinctive pattern of chronic inflammation
Seen in limited number of infectious and some non-infectious conditions
What characterizes granulomatous inflammation?
Characterized by aggregates of activated macrophages having a squamous cell-like (epithelioid) appearance
Cellular attempt to contain an offending agent that is difficult to eradicate, such as indigestible substances
What is a bacterial granulomatous inflammation?
Mycobacteria - tuberculosis
What is an autoinflammatory granulomatous inflammation?
Sarcoidosis
What is the most common necrosis to see with TB?
Caseous necrosis
What is required for diagnosis of sarcoidosis on biopsy?
Non-caseous granulomas
Where can granulomatous inflammation form?
Can form in setting of persistent T cell responses to certain microbes and fungi
What are the mechanisms of granulomatous inflammation?
- Th1 cells secrete gamma IFN which activates macrophages
- Macrophages release TNF-alpha which induces and maintains granuloma formation
What do anti-TNF drugs cause as a side effect? What is it important to test for before starting anti-TNF therapy?
Causes sequestering granuloma to breakdown, leading to disseminated disease
Always test for latest TB before starting anti-TNF therapy
What are indications for anti-TNF drugs?
Rheumatoid arthritis
Psoriasis
Crohn’s Disease
What is a granuloma?
Focal area of granulomatous inflammation
Consists of microscopic aggregation of macrophages that are transformed into epithelial like cells (epithelioid cells)
Epithelioid cells are surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells
What is the histological appearance of granulation tissue?
- Proliferation of fibroblasts
- New thin-walled, delicate capillaries - see RBC’s
- Fibroblasts and capillaries are in a loose ECM
- Scattered macrophages and some other inflammatory cells (in earlier stage of granulation tissue, numerous macrophages can be seen)
What does granulation tissue consist of?
Fibroblasts surrounded by abundant extracellular matrix, newly formed blood vessels, and scattered macrophages and some other inflammatory cells
Cells in granulomas may fuse to form ___
Multinucleated giant cells
What are the two arrangements of multinucleated giant cells and what is the arrangement based on?
Arrangement based on the nuclei arrangement
- Peripheral arrangement - Langhans-type
- Haphazard arrangement - foreign body-type
What is a langhans giant cell?
Associated with inflammation
Giant cell
What is langerhans?
Used to describe normal islets of langerhans (in pancreas) or normal dendritic cells in skin, mucosa or lymph node (Langerhans cells)
What are foreign body granulomas?
Form in response to inert foreign bodies: splinter, suture material, breast implant, piece of glass, etc.
Forms when material too large to be phagocytosed by single macrophage
Foreign material often can be seen inside granuloma
Offending agent walled off, but not usually killed or eliminated
What is lymphangitis?
Inflammation of lymphatic channels
Leukocytes and cell debris in lymphatics
Red streaks up the arm are commonly called “blood poisoning”
What is reactive lymphadenitis?
Inflammation of draining lymph nodes
If infection overwhelms lymph nodes, may gain access to vascular circulation: bacteremia
What are systemic effects of inflammation collectively called?
Acute Phase Response
Systemic Inflammatory Response System (SIRS)
Regulated pathophysiological reaction
What are the clinical signs of systemic effects of inflammation?
Fever, changes in serum acute phase proteins, increased WBCs, decreased appetite and altered sleep patterns
Systemic changes secondary to cytokines, which are stimulated by bacterial LPS and other inflammatory stimuli
How is fever produced? Why is it important?
Clinical hallmark when due to infection
Bacterial products such as LPS (exogenous pyrogen) and stimulate production of IL-1, TNF (endogenous pyrogens)
IL-1 and TNF increase cyclooxygenase (COX)
How do IL-1 and TNF lead to fever?
IL-1 and TNF increases cyclooxygenase (COX) and stimulate PG synthesis in hypothalamic thermoregulatory center (vascular cells and perivascular cells)
PG, especially PGE2, stimulates production of neurotransmitters that reset body thermometer
