Inflammation II Flashcards
what cell type is mainly associated with acute inflammatory infiltrate?
neutrophils
what disease processes are associated with acute inflammatory infiltrate?
- infections like bacterial pneumonia or pyelonephritis 2. diseases associated with tissue necrosis 3. foreign bodies 4. immune mediated disease (ex IBD)
what disease processes are associated with tissue necrosis
MI from ischemia, acute appendicitis, trauma, physical or chemical injury
what characteristics do all acute inflammatory reactions have?
- dilation of small blood vessels 2. stasis 3. vascular permeability
what does vascular permeability lead to?
- accumulation of leukocytes in extravascular tissues 2. accumulation of fluid in extravascular tissues and body cavities (edema)
what is an effusion?
accumulation of fluid or purulent material in body cavities
what is found in acute bacterial pneumonia?
congested septal capillaries and extensive neutrophil exudation into alveoli, early red hepatization
what happens with acute appendicitis
may occur with obstruction of lumen from fecalith or other cause. increased intraluminal pressure will impair venous outflow resulting in ischemia and stasis of luminal contents. bacterial proliferation will ensue.
what is transudate
filtrate of plasma caused by abnormal increase in hydrostatic pressure or decrease in plasma oncotic pressure that is NOT ASSOCIATED WITH INCREASE IN VASCULAR PERMEABILITY
what are some causes of transudate?
congestive heart failure, liver failure
what is the makeup of transudate?
low protein content specific gravity is less than 1.012 have very few ABC no cellular debris
what is exudate?
results from increase in blood vessel permeability characteristic of inflammation
what is pus?
exudate rich in neutrophils, debris of dead cells, microbes
what is the makeup of exudate?
contains cellular and chemical mediators critical to inflammation high protein content specific gravity is greater than 1.020 contains cellular debris
what are morphological patterns of acute inflammation?
- serous inflammation 2. fibrinous inflammation 3. suppurative or purulent inflammation 4. abscess 5. ulcers
what is serous inflammation ?
outpouring of thin, clear or straw colored fluid derived from plasma or secreted by mesothelial cells lining a body cavity (minimal cells)
what is serosanguinous
pink tinged serous fluid due to presence of small amt of blood
what are possible causes of serous inflammation?
burns, viral infections
what is fibrinous inflammation
larger molecules such as fibrinogen pass through the vascular barrier and fibrin is deposited in extracellular space, looks like white strings
what is suppurative/purulent inflammation
characterized by production of large amounts of pus containing neutrophils, liquefactive necrotic cells, and exudate associated with certain types of pyogenic bacteria
why does tissue necrosis occur?
injurious stimulus causes inflammatory response which harms the tissue itself bc of enzymes and ROS
what is empyema
purulent exudate in pleural cavity that is usually associated with bacterial pneumonia
what are abscesses?
localized collections of purulent and necrotic material
how do abscesses form?
neutrophils within pus secrete enzymes that digest and destroy involved tissues, and the resultant cavity is filled with pus and necrotic tissue.
what is the center of the abscess filled with?
necrotic neutrophils, bacteria, tissue
what is on the periphery of abscess?
preserved neutrophils surround necrotic focus
what surrounds the abscess?
fibroblastic proliferation may form fibrous capsule, and abscess may be walled off and be replaced by connective tissue
what is a possible outcome of abscesses?
collapse of the cavity followed by healing through scar formation. but if it cannot do this bc inflammatory response is inadequate or lack of Abx, microorganisms will break out of the abscess and disseminate via bloodstream (sepsis)
what is an ulcer
local defect of the surface of an organ (usually epithelial tissue) produced by sloughing of inflamed necrotic tissue
what are 3 outcomes of acute inflammation?
- resolution with regeneration 2. resolution with scarring 3. progression to chronic inflammation
what occurs in resolution with regeneration?
tissue returns to normal in both morphology and function
when can tissues resolve with regeneration?
when injury is short lived and there is lack of major tissue destruction
what occurs in resolution with scarring?
healing by connective tissue replacement (fibrosis, scarring)
when can tissues resolve with scarring
when substantial tissue destruction has occurred and/or if injured tissue is incapable of regeneration
what occurs in progression to chronic inflammation
the inflammatory response cannot be resolves either because of persistence of injurious agent of interference with normal healing
what are adhesions?
thin bands of collagenous connective tissue that restrict motion or cause retraction of internal organ to abnormal position
how long does chronic inflammation last?
weeks, months or years
how long does acute inflammation last?
48hours
when can chronic inflammation arise?
following acute inflammation that does not resolve like when injurious agent persists with ongoing tissue damage OR without acute inflammation
what are major causes of chronic inflammation?
- directly following bout of acute inflammation 2. persistent infections 3. infections with certain organisms 4. immune mediated inflammatory diseases 5. response to foreign material or toxins 6. response to malignant tumors
what organisms are most likely to cause chronic inflammation?
mycobacteria and some atypical bacteria, viral, parasitic and fungal infections
example of chronic inflammation caused by foreign material or toxins
coal miners lung, silicosis, atherosclerosis due to persistent hypercholesterolemia
what cell types are associated with chronic inflammation?
mononuclear inflammatory cells like macrophages, lymphocytes and plasma cells – not neutrophils
what causes tissue destruction in chronic inflammation
both mononuclear inflammatory cells as well as by persisting offending agent
how does tissue heal in chronic inflammation
fibrosis (scar formation)
what other inflammatory cells are seen in chronic inflammation
- eosinophils 2. mast cells
describe inflammatory effects of mast cells
widely distribute in connective tissues and participate in acute (anaphylaxis) and chronic inflammation
how do eosinophils cause damage
major basic protein is secreted and is toxic to parasites but also lyses epithelial cells contributing to tissue damage
development of macrophage
monoblast–>monocyte–>macrophage
describe the change of cell type from acute to chronic
when chronic inflammation is following acute inflammation, monocyte will be predominant type extravasating from blood vessels at about 48hours after onset of acute inflammatory process, replaces the neutrophil
what cell type replaces neutrophil after acute inflammatory reaction?
monocyte
what classically activates macrophages?
microbes and IFNgamma
what alternatively activates macrophages?
IL-13 IL-4
what is the function of classically activated macrophages? M1
- release ROS, NO and lysosomal enzymes for killing 2. release IL-1, IL-12, IL-23 and chemokines for inflammation
what is the function of alternatively activated macrophages? M2
repair and anti-inflammatory 1. release GF and TGFbeta for tissue repair and fibrosis 2. release IL-10 and TGFbeta for anti-inflammatory effects
functions of macrophages
- ingest microbes and dead tissue 2. initiate tissue repair 3. secrete inflammatory mediators 4. display antigens to T lymphocytes and respond to T cell signals between lymphocytes and macrophages
what activates T and B lymphocytes ?
microbes and environmental Ags,
what do lymphocytes do in chronic inflammation?
amplify and propagate chronic inflammation
what do Th1 cells secrete?
IFN gamma, which activates macrophages via classical pathway
what do Th2 cells secrete
IL-4, IL-5, IL-13, which activates eosinophils and macrophages via alternative pathway
what do Th17 cells secrete?
IL-17 and other cytokines, indices secretions of chemokines that recruit neutrophils and monocytes
what does chronic inflammation look like?
dense infiltrate, monocytes and plasma cells, macrophages, lymphocytes
what is seen in viral pneumonia?
lymphocytes are seen in interstitium (also atypical bacteria like mycoplasma and chlamydia)
viral or atypical bacterial pneumonias have interstitial lymphocytic infiltrate.
interstitial pneumona – inflammatory infiltrate is primary lymphocytes and is in alveolar septa
what is seen in bacterial pneumonia?
neutrophilic intraalveolar infiltrate
more pink
what bacterial infections can cause acute bacterial pneumonia?
strep pneumo, staph aureus, h. influenzae, klebsiella pneumoniae
what is granulomatous inflammation
distinctive pattern of chronic inflammation characterized by focal aggregates of modified macrophages called epithelioid cells and multinucleated giant cells, usually surrounded by rim of lymphocytes
what cells are characteristic in granulomatous inflammation?
epithelioid cells and multinucleated giant cells
what is a granuloma
focal aggregate of macrophages
2 types of granulomas
- immune granuloma
- foreign body granuloma
what 2 conditions do immune granulomas develop?
- macrophages phagocytose a substance they are unable to degrade
- indigestible substance is immunogeneic and induces T cell mediated response
what substances are usually not degradable by macrophages?
microorganisms like mycobacterium tuberculosis or fungi like histoplasma capsulatum
what does induction of T cell mediated response in an indigestible/immunogenic substance lead to?
transformation of macrophages into epithelioid cells
what are the components of immune granulomas?
- epithelioid cells
- langhans type giant cells
- rim of lymphocytes, plasma cells, and fibroblasts
what are epithelioid cells?
macrophages that resemble epithelial cells
what are langhans-type giant cells?
huge cells formed by the fusion of many epithelioid macrophages that have a voluminous cytoplasm with up to 50 macrophage nuclei within arranged around the periphery
what is on the rim of immune granulomas?
lymphocytes, plasma cells, fibroblasts
what is a classic feature of TB granulomas?
necrotic center (caseous necrosis)
what type of hypersensitivity reaction gives rise to the development of granulomas>
type IV
illustrates the role of Th1 cytokines in granuolmas, Th2 cells in lesions.
what causes foreign body granulomas?
substances are too large to be phagocytosed by a single macrophage
or
substances not capable of eliciting a T cells mediated immune response
so multiple macrophages and giant cells surround the foreign body
examples of foreign bodies capable of causing foreign body granulomas?`
talc, asbestos, silica, surgical sutures
what cells surround the foreign body in FB granuomas?
multiple macrophages and giant cells
what do giant cells look like in a foreign body granuloma?
nuclei are arranged haphazardly througout the cytoplasm
(vs peripheral arrangement of langhans type giant cells)
what do giant cells look like in immune granuolmas?
nuclei are arranged at the periphery like a “C”
what do foreign body granulomas look like?
- giant cells have nuclei arranged haphazardly in cytoplasm
- may or may not have surrounding rim of other inflammatory cells
- can usually see foreign body in the center
