12. Chronic Inflammation II Flashcards
Cells in chronic inflam > ____ (neutrophils in acute inflam)
Macro’s need help > T cells
Macro engulfs, and will try to kill it themselves (not very good at it) > produce ____ > present on material of cell on surface > present antigens to T cells > activating ____: neutrophil recruitment and some monocyte; activate Th1: ____ > macrophages (classical); bi-directional mode of activation as long as etiology exists
macrophages
cytokines
TH17
IFNgamma
Chronic Sialadentitis
Histo of normal salivary gland in middle
Chronic: foci of ____ cells; stain with trichrome and parts would be blue > destruction, ____, and foci of inflam cells, and fibrosis all going on simultaneously
inflam
LOF
Rheumatoid Arthritis
Chronic > pannus formation (___ cells, ___ cells, ___ tissue, ___ connective tissue), and fibrous connective tissue > fibrous ankylosis (___ fused with fibrous tissue), and another example, which involves the use of bony joints
proliferating synovial lining
inflammatory
granulation
fibrous
Liver failure > most likely to be ___
transudate
Exposed to silica dust particles > lung tissue > normal lung parenchyma replaced with ___ > ___
fibrosis
LOF
Granulomatous Inflammation • Infectious: – \_\_\_ (Bacterial) – \_\_\_, Blastomycosis (Fungal) – \_\_\_ disease (Bacterial)
• Non-Infectious (foreign-body):
– ___, breast prosthesis,
– ___, food particles, ___
• Unknown:
– ___
– Orofacial granulomatosis
How is granulomatous different from non-specific chronic inflammation > in chronic: destruction taking place in a large area
Destruction here doesn’t occur uniformly, you begin to see small nodules
Where the inflam reaction is trying to contain the etiology > make sure that it doesn’t get out of hand
Most etiologic agents for GI are agents that are hard to remove, or agents that are very difficult to digest (macro’s take intracellularly, they can’t and then they induce granulomatous inflammation)
tuberculosis histoplasmosis crohn suture uric acid (gout) metals
sarcoidosis
Granulomatous Inflammation
- A distinct pattern of chronic inflammation characterized by the presence of ___
- A small nodular collection in which the predominant cell is the activated ___
• Epithelioid cells – Derived from \_\_\_ – \_\_\_ cytoplasm – Long \_\_\_ nuclei • Surrounded by a collar of \_\_\_ (and fibroblasts)
Activated macrophage > epithelioid cells > look like epithelial cells (have pink cytoplasm, but unlike epithelial, their nuclei is ___)
granulomas macrophage macrophages pink stringy "round cells"
string-like
Granulomatous Inflammation
- Giant Cells:
- “Committee of ___ cells
- > ___ um in diameter
- Abundant Cytoplasm
• Langhan’s type
– ___ or more nuclei in periphery
– “___ pattern”
• Foreign body:
– Nuclei ___
– “___ Pizza”
- ___ bodies
- ___ bodies
Giant cells are not always present > base your assessment on presence of ___
When macrophages are trying to rid of inorganic material (suture) > you also see a committee, but arranged in a pepperoni pizza (foreign body)
___ contrition > schaumann body
___ > asteroid body
epitheloid 50 20 horse shoe scattered pepperoni schaumann asteroid
granuloma
calcium
asteroid/star-shaped
You see a lot of ___ in CGD
In biospy of proud flesh > ___ tissue
PA granuloma > chronic inflam ___ tissue
These are all misnomers; when you have a granulomotous inflammation > you see the structure of a physical ___, and not examples like this
These are not examples of ___ inflammation (must have giant cells, epitheliod cells, etc.)
neutrophils/macro’s
granulation
granulomatous
granuloma
granuolomatous
Tuberculosis
Tuberculosis:
It is a disease of poverty - people of lower socioeconomic status and overcrowding
◦ Now about 1.7 billion people worldwide have been infected
‣ But infection doesn’t automatically mean ___
• Ex: Septa can be crowded and if infected person with Tuberculosis sneezes around you, you can become ___ but not ___
disease
infected
diseased
Tuberculosis
Receptors are present on ___ (not many neutrophils in alveolar space)
Takes in the microbacterium and tries to digest it > MB has something in it that prevents the macrophage from digesting it > ___ is activated, however it is ineffective and you cannot release lysosomal enzymes
The microbes multiply within the phagolysosome, and then released into the ___ > bacteremia seeding into multiple sites; this occurs 1-3 weeks after infection (may have ___ symptoms, or ___)
If ___ immune is not activated in response > trouble
Cell-mediated response tries to now contain bacterium:
___ macro’s present on MHC II > T-cells > Th1 > IFNgamma > ___ > they’re able to kill microbes by producing more chemokines/cytokines > macrophages transform into ___ cells > granuloma > can undergo ___
macrophages phagolysosome lung flu-like asymptomatic
cell-mediated
alveolar
macrophages (classical)
epitheloid
caseation
Tuberculosis
Primary infection takes place in area where microbe’s first lodged and in draining lymph node > ___ > granulomas coalesce > ___ necrosis > ___ complex:
Infected with microbacterium, organisms in lung > alveolar macro’s trying to digest, but bacteria prevent and escape > activate T-cells; granuloma occuring at site of ___ and the ___
If you have a good immune system > T/macro’s > contains the microbe > healing by ___ (this is good, no symptoms or disease, do not want to remove)
Individuals who are infected with HIV/AIDs > defective T-cell number > not able to contain microbe, and the lesion becomes ___ Tb > can occur as a result of reinfection, or reactivation > disease-state >
Can now become progressive and spread to other areas > ___ Tb
No T cells > defense mechanism compromised > cavitation > localized ___ obstructive lesions
Lung biospy > ___ staining to detect organisms > other conditions may mimic symptoms associated with Tb > histoplasmosis, coccidoiodomycosis and blastomycosis > ___ infection
caseation coag Ghon nucleation lymph node
scar
secondary
milliary
caseating
acid-fast
fungal
Histoplasmosis, Coccidiodomycosis and Blastomycosis
• Histoplasmosis:
– Most ___ systemic fungal infection in the US
– ~500,000 new cases every year:
– ___ areas with soil enriched with bird or bat ___
– Fertile river valleys; ___, ___
• Coccidiodomycosis:
– ___ part of the US
– California’s San Joaquin Valley (“___”)
• Blastomycosis:
– Overlap with ___
– Relatively ___ (1/10th of Histoplasmosis)
Top-right > CM
Bottom-left > BM; bigger cell
common humid excrement ohio mississippi
southwestern
valley fever
histoplasmosis
uncommon
Histoplasmosis
• Primary:
– ___ (fever, headache, ___ cough)
• Chronic (granulomatous):
– ___ (less common than primary)
– Similar to ___ (cough, weight loss, fever, weakness)
• Disseminated: – Spread of infection from lung – \_\_\_, AIDS – \_\_\_, GI, liver, \_\_\_ – Commonly affected: \_\_\_, \_\_\_, \_\_\_ mucosa
Ulcerated granular lesion; maxillary buccal vestibule. ___?
Ulceration: Ventral surface of the tongue. ___?
self-limited
non-productive
lung
Tb
immunosuppressed kidneys oral mucosa tongue palate buccal
cancer
cancer
Histoplasmosis
Diagnosis, Treatment and Prognosis:
• Diagnosis:
– Identification of organism in tissue section or by culture
– Serologic testing: ___
• Primary:
– self-limiting-no ___ required
• Chronic (granulomatous):
– ___/Itraconazole
• Disseminated: – Death in 80-90 % of \_\_\_ patients, if untreated – \_\_\_ then \_\_\_ (daily, 6 – 18 months) – Despite therapy, mortality rate, (7 -23%)
Medium power: ___ containing organisms (arrows)
High power: yeasts of His. cap ___ stain
antibodies
amphotericin B
immuno-suppressed
amphotericin B
itraconazole
macrophages
grocott-gomori methenamine silver
Blastomycosis
• Primary:
– Resemble ___; high fever, chest pain,
night sweats, ___ sputum.
• Chronic (Granulomatous):
– Lung (More ___ than primary)
– Similar to Tb (cough, weight loss, fever, weakness)
• Disseminated: – Spread of infection from lung – \_\_\_ – Epithelial hyperplasia (\_\_\_ carcinoma?) – Oral lesions (from \_\_\_ or local \_\_\_)
rregular ulceration of the tongue:
Chewing ___ “Kentucky field candy”
pneumonia
mucopurulent
common
severe cutaneous infection
squamous-cell
lung
inoculation
Blastomycosis
Blastomycosis
• Oral lesions (continued…)
– Mass on ___ mucosa
• Diagnosis:
– Identification of organism in tissue section
– Culture specimen from sputum or fresh biopsy material
– ___ testing NOT helpful (lack of specific antibody)
– ___ probe
• Primary:
– self-limiting-no ___ required
• Chronic:
– ___/ Itraconazole
• Disseminated:
– Only occurs in a small percentage of infected patients.
– Prognosis ___ with treatment
– High mortality rate in ___ and patients with AIDS
Presence of ___ cell in high-power
Use ___agents to treat
High power: large yeast of ___. and multinucleated giant cell
buccal
serologic
DNA
treatment
amphotericin B
good
immunosuppressed
giant cell
anti-fungals
Blas. Derm.
Crohn Disease
• Inflammatory bowel Disease (IBD):
• Ulcerative colitis
– ___ and rectum
– ___ and submucosa
• Crohn Disease – May involve any are of the \_\_\_ tract – Transmural – Abdominal \_\_\_, diarrhea, \_\_\_ – \_\_\_ appearance – \_\_\_ granuloma
Chron’s > any area of the GI tract > it crosses into the lower layers (___)
Unlike Tb, in Chron’s the granulomas are ___ > do not form cheese-like structure within the granuloma
colon mucosa GI cramping nausea cobblestone non-caseating
transmural
non-caseating
Crohn Disease
Oral before \_\_\_ lesions in ~30% of cases. • Swelling of the \_\_\_ • \_\_\_----buccal mucosa • \_\_\_ granuloma
If you think it’s Chron’s > ask for ___
buccal lips cobblestone non-caseating symptoms
Crohn Disease
Autophagy/Inflammasome/Granulomatous inflammation?
- Healthy ileum: ___ cells secrete antimicrobial peptides and lysozyme to control intestinal microbiota.
- ___: cellular homeostatic process in which “autophagosomes” degrade captured proteins and cytoplasmic organelles
- Loss of autophagy caused by ATG16L1 mutation, fewer granule content
- Loss of autophagy in macrophages from ATG16L1 mutation results in overproduction of ___
LOA > interaction bt autophagy and inflammasome pathway > autophagy inhibits the ___ pathway
If autophagy is gone > inflammasome is ___ > macrophages produce IL-1b
paneth
autophagy
IL-1B
inflammasome
upregulated
Granulomatous Inflammation
• Infectious:
– Tuberculosis (Bacterial)
– Histoplasmosis, Blastomycosis (Fungal)
– Crohn disease (Bacterial)
• ___ (foreign-body):
– Suture, breast prosthesis,
– Uric acid (gout), food particles, Metals
• Unknown Etiology: – Sarcoidosis
– Orofacial granulomatosis
Non-infectious
GRANULOMATOUS INFLAMMATION
Non-infectious (foreign-body): ___
Breast implant leaks > ___ particles > macro’s try to digest and remove, however they are unable to do so > ___ inflam
Silica particles in cross-section; foreign body granuloma, and the giant cells are ___ shaped
breast prosthesis
silica
granulomatous
pepperoni
GRANULOMATOUS INFLAMMATION (Non-Infectious)
Polarized light: Intravenous drug user (drug mixed with talc)
Cholesterol clefts with associated foreign-body giant cells
Giant cell (___)
___ > cells are dying and they are releasing lipid mediators
pepperoni
cholesterol clefts
Granulomatous Inflammation • Infectious: – Tuberculosis (Bacterial) – Histoplasmosis, Blastomycosis (Fungal) – Crohn disease (Bacterial) • Non-Infectious (foreign-body): – Suture, breast prosthesis, – Uric acid (gout), food particles, Metals • \_\_\_: – Sarcoidosis – Orofacial granulomatosis
unknown etiology
Sarcoidosis
- Multi-system disorder of ___ etiology characterized by ___ granulomatous inflammation in many tissues and organs
- World-wide distribution
- Age, <40; ___ Americans
- ___ 10 times higher than whites
• Primary:
– Fever, fatigue, ___, weight loss
• Chronic (Granulomatous): • \_\_\_ ~90% – \_\_\_, dry cough, chest pain • \_\_\_ ~20% – Chronic \_\_\_, indurated lesions termed “\_\_\_” – \_\_\_, nose, \_\_\_ and face • Salivary gland enlargement: – \_\_\_
Some sort of ___ involvement
Symptoms are similar to ___
Chronic violaceous > ___; indurated > hard
unknown
non-caseating
danish/swedish
african americans
anorexia
lung dyspnea cutaneous violaceous lupus perino ear lips xerostomia
genetic
TB
red
Sarcoidosis
• Oral:
– ___, ___ labial mucosa
• Salivary gland enlargement: – ___
Multiple ___ Macules
Erythematous macule with central ___
Macule > discolored lesion that is not raised (redness)
Lips > erythematous macule > central hyperkeratosis (area within the middle of the macule)
hard palate
lower
xerostomia
erythemetous
hyperkeratosis
Sarcoidosis
• Histopathology: • Classic granulomatous inflammation • \_\_\_ cells • Do not typically undergo central \_\_\_ necrosis • Asteroid bodies – Entrapped fragments of \_\_\_ • \_\_\_ body • Fungal or bacterial stains \_\_\_
Full blown Tb > cough out material; SD > the cough will be ___
Can differentiated from HP and fungal diseases and Tb (bc ___ for fungal and bacterial stains)
giant caseous collagen schaumann negative dry negative
Diagnosis and Treatment of Sarcoidosis
- Clinical and Radiographic
- Histologic
- ACE
- Pulmonary involvement
- Kveim Test
- 60% resolve within 2 years
- Corticosteriods
- Methotrexate
- TNF-a antagonists
Can see SD on ___
ACE > ___
Kveim test > injected sterile ___ (___) tissue into skin and waiting to see a development of a ___
Majority of patients resolve within ___ yrs
Bc of inflam > ___
Methotrexate > ___
TNFa antagonists do not always ___
x-ray elevated sarcoid spleen granuloma
2
corticosteroids
anti-metabolite
work
OROFACIAL GRANULOMATOSIS
Melkersson-Rosenthal Syndrome
Non-___ Persistent swelling of one or both ___
Persistent enlargement of lower lips ___ PARALYSIS
___ tongue
tender
lips
facial
fissured
OROFACIAL GRANULOMATOSIS
• Cheilitis Granulomatosa – Swelling of ___ only
Only swelling of lip, and on biopsy only on part of lip > cheilitis > granulomastose > no ___ paralysis or ___ tongue
lips
facial
fissured
Diagnosis
- ___ granulomatous inflammation
- Edema
- No ___ material
Granulomas contain multinucleated giant cells within granulomas
Presence of edema > swelling
Unknown etiology, no foreign material
Clinical manifestations, based on biopsy, and swelling is due to an edema (unknown which ___)
non-caseating
foreign
type
Treatment
- ___
- Antibiotics?
- Surgical ___
Unknown etiology > target the lesion directly
Will not use antibiotics (amox) because it’s not a typical ___ infection
___ > medium to high potent corticosteroid
intralesional steroid
recontouring
microbial
triamcinolone
Inflammation and Wound Healing
Inflammation • Wall off the \_\_\_ agent, • Eliminate the cause of \_\_\_, • Minimize the extent of tissue damage, • \_\_\_ dead cells and debris, • Initiate healing,
Inflammation > trigger: dead tissue, necrotic tissue, temperature and bacterial
Vascular response > ___, and ___; cellular response (neutrophils)
In order to initiate healing you need inflammation, which is also a vascular response (need ___ tissue formation) > ___
Wound healing and chronic inflammation > ___ tissue is wound healing, but it becomes extensive that affects function of organ > chronic inflammation > healing is complete until the etiology is removed
Non-specific inflam > neutro recruitment, tissue damage, fibrosis > foci of inflam cells and tissue destruction (chronic sialodentitis); silicosis
Granulomatose > have distinct phenotypes
injurious
injury
remove
vasodilation/constriction
vascular permeability
granulation
angiogenesis
scar
