Pathology of Chronic Inflammation Flashcards
Outsomes of acute inflammation
resolution
healing by fibrosis
CHRONIC INFLAMMATION
Note that whith chronic injury we might see angiogenesis rather than vasodilation
Causes of chronic inflammation
Persistant infections ( organisms difficult to eradicate. Ex TB, fungal infections, parasites)
Prolonged exposure to toxic agents
neurodegenerative diseases (ex alzheimers)
Metabolic syndome (ex NIDDM)
Cancer
cardiovascular diseases
hypersensativity diseases
Normal lung. On the mid right side you can see that there is simple squamous through which there is gas exchange in alveolar space
Necrotic TB lung
You can see on the R side there are areas of necrosis
You can also see epithelioid macrophages
No alveolar spaces means that you can not have gas exchange
Up close of TB lung
You can see the necrosis on the R
this is caseous necrosis
You also see some macrophages
Granulomatous inflammation in tuberculosis is characterized by collection of cells that are often activated by
Macrophages
T lymphocytes
B lymphocytes
Neutrophils
Eosinophils
T lymphocytes
Cells in chronic inflammation
Stimulates macrophages -> leads to granulomatous infection
Persistent infections
Immune granulomas are caused when the inciting agent is difficult to eradicate, such as a persistent microbe or self antigen
Sarcoidosis
systematic granulomatous disease of unknown cause that may involve many different tissues and organs
prolonged chronic inflammation leads to fibrosis of the pulmonary interstitium
bilateral hilar lymphadenopathy or lung involvement is most common occuring 90% of cases
Disordered immune regulation in genetically predisposes individuals
involved tissues contain well formed nonnecrotizing granulomas
Sarcoidosis
Sarcoidosis lung. You can see that this is really different. The dark purple cells are lymphocytes
Notice the circle of cells in the top R corner. This is a langhans. Bunch of cells fused together commonly found in granulomatous conditions
Sarcoidosis lung
note that there is a lot of fibrosis and lots of inflammation
Cells most commonly associated with chronic inflammation
macrophages
neutrophils
eosinophils
mast cells
basophils
MACROPHAGES
neutrophils primarily seen in active inflammation
eosinophils primarily seen in allergic reactions
Mast cells most commonly seen in allergies and anaphylaxis
basophils seen same as mast cells
Macrophage effector function
In circulatino macrophages are monocytes
in tissues macrophages are macrophages
Some macrophages are resident (liver, lung)
two pathways for macrophage
M1 pathway/ classical activaiton of macrophages
microbes and cytokine (INF gamma) stimulates this
mainly involved in inflammation and tissue injury
M2/ alternative pathway of macrophage activation
IL4 and other cytokines do this
mainly involved in repair
What stimulates M1 (classical) macrophage activation
microbes
cytokines (INF gamma)
What stimulates M2 (alternative) macrophage activation pathway
IL-4
other cytokines
Hypersensativity diseases
excessive and inappropriate activation of the immune system
immune reactions develop against the individuals own tissues, leading to autoimmune diseases
immune responses against common environmental substances are the cause of allergic diseases, such as bronchial asthma
reactions serve no useful purpose and only cause disease
Crohn’s disease
unknown pathogenesis but probably involves a combination of environmental factors, abnormalities in immune regulation, and a genetic predisposition
segmental disease involving a variable extent of the colonic mucosa and wall
cancer risk correlates poitively with diease duration and the anatomic extent of the inflammatory provess
( if you can not control this you have a higher risk for cancer)
Normal colon.
You can see that this looks similar to glandular
Small purple nuclei line the apical cytoplasm
Seccretes mucin
Abnormal colon. Associated with IBD.
Colonic ctypt architecture destroyed
neuclei are enlarged/ reactive
TONS of inflammatory cells in here
Colorectal adenocarcinoma
Looks like the glands are shaped irregularly
IBD associated colorectal cancer
you can see on the bottom part of the pic that the glands have invaded the muscularis
The most likely process cancer arises in the setting of chronic inflammation
increase DNA repair
increase apoptosis
decrease cell proliferation
increase DNA damage
INCREASE IN DNA DAMAGE
Ulcerative colitis and crohn’s dz
Inflammatory bowel disease
persistent immune response to normal flora
activated macrophages and CD4+ T cells secrete cytokines, prostaglandins, leukotrienes, NO
characterized by diarrhea, rectal bleeding, and weight loss
Increased risk for colorectal cancer
Notice that inflammation can cause release of free radicals and cytokines
these can both turn on NF-kB and activate Cox-2
There both inhibit apoptosis and lead to cell proliferation
Foreign body granuloma
you can see that there is fibrosis and that there are macrophages around these white structures
turns out that the white structures are foreign body (in this case suture material from carpel tunnel surgery)
some of the macrophages on bottom R are multinucleated
Foreign body granuloma
biologic response to relatively inert foreign bodies
in the absence of T cell-mediated immune responses, it is macrophage mediated
granulomas form around material such as talc, sutures, implants, or other fibers that are large enough to preculde phagocytosis by a macrophage
there materials do not incite any specific inflammation of immune response
Granulomatous inflammation in this case (suture foreign body material) is characterized by collection of cells that are often activated by
macrophages
T lymphocytes
B lymphocytes
Neutrphils
none of the above
MACROPHAGES
Atheroslerosis
fatty streak formation- contains lipid filled macrophages (foam cells) and activated T cells
fibrous cap- advanced stage to wall off lesion
endothelial damage
plaque rupture- material inside plaque released, thrombosis occurs
treated by statins- decrease leukocyte adhesion and NO, inhibits cholesterol synthesis
Aorta
Smooth muscle wall of the aorta
Aneurysm
localized abdominal dilation of a blood vessel
abdominal aortic aneurysm
This form (AAA from atherosclerosis) is through to arise from
prolonged exposure to potentially toxic agents
persistant infections
hypersensativity diseases
metabolic syndrome
Prolonged exposure to potentially toxic agents
