2-Chronic Inflammatory Flashcards
chronic inflamm
def
must be > 2 weeks, low grade smoldering resp either after acute or from repeated episodes of acute
must have 1. inflamm 2. tissue destruction 3. attempts at repair
-inflamm with mononucleocytes
-repair with fibroblasts
causes
- persistent microbial infections- low pathogenicity so not kill you right away so delayed hypersensitivity and hard to eradicate
- immune related inflamm disease- autoimmune, unregulated responses, allergic vs environ antigens
- prolonged exposure to toxins - exo or endogenous (inc plasma lipid components)
morphological features
- infiltration with mononuclear cells aka macrophages, lymphocytes, plasma cells
- tissue destruction- induced by persistent stimulus or inflamm cells
- attempts healing- CT replace damaged tissue, new vessel prolif aka angiogenesis and fibrosis (collagen)
role of macrophages
key cell in chronic and granulomatous inflamm
-filter and sentinels for lympho stimulation
from circulating blood monocytes that emigrate to site of injury 24-48 hrs after onset
different types of macros
@ liver = Kupffer cells
@ spleen, LNs, lungs = pulmonary or alveolar macros
@ CNS = microglia
@ bone = osteoclasts
features for activated macros
- inc size (look large and flat like squamous)
- inc number lysosomes
- inc amount of lyso enz
- inc ability to kill orgs
compared to monocytes
activation signals macros
- cytokines from act T cells and NK cells
- bacterial endotoxins, gram neg
- microbial products
- other inflamm mediators
macro activation pathway
- circulating mono will extravate into tissue
- interact with act IFN-gamma or microbes from T cell > inflamm OR IL4/cyotkines > repair
- if inflamm then ROS, proteases, cytokines, coag factors, AA metabolites
- if repair then growth factors, fibrogenic cytokines, angeiogenic factors, remodelling
macrophage products
inflamm
1.
macrophage products
repair
persistence of macros
- cont recruitment of new
- local prolif of existing at site of inflamm
local effects of macros
from TNF/IL1 activation
1. vascular endo inc procoagulant activity and IL1 cytokines = inflam
2. act leukocytes to produce cytokines = inflam
3. fibroblast act and inc collagen= repair
systemic effects of macros
lymphocytes
mobilized in setting of specific immune stim like infections and non-immune inflamm like trauma
reciprocal relationship
macro-T cell
activated T cell expresses TNF, IL17, chemokines to recruit neutrophils or macros that get activated by IFN-gamma
act macrophage secretes IL1 and TNF-alpha
antigen presentation to T cells by IL12 (TH1)
plasma cells
terminal product of B cell act that prod antibodies vs persistent antigens @ inflamm site or vs altered tissue components
can see golgi ghost and large dense nucleus
eosinophils
parasitic infections or immune rxn by IgE with allergies
recruitment dep on chemokine eotaxin
granules have major basic protein toxic to parasites but also can epithelial cell lysis
mast cells
both acute and chronic inflamm
armed w/ IgE to certain antigens and will release histamine and PG so central for anaphylactic rxns
helpful in parasitic infections bc may produce cytokines like TNF for fibrosis
neutrophils
in chronic bc of persistent microbes or mediators enhanced by macrophages, necrotic cells, T cells
acute and chronic can co-exist as chronic active inflamm
key cell of acute
results of chronic
cont tissue damage
ongoing
lifestyle factors
- smoking
- xs alc intake
- physical emo stress
- obesity
- lack of exercise
- diet
granulomatous inflamm
distinctive pattern of chronic in limited # of infections
granulom inflamm characteristics
aggs of act macroswith squamous cell appearance aka epithelioid, focal area of the inflamm is granuloma surrounded by collar of mononuclear leuks (lymphocytes, plasma cells)
cellular attempt to contain offending agent diff to eradicate like indigestible substances
extensive tissue destruction (caseous necrosis) sometimes
conditions
- bacterial infection- tuberculosis (caseous necrosis)
- fungal
- parasitic
- autoinflamm- sarcoidosis
- foreign materials
settings of persistent T cell respons to certainmicrobes and fungi
granulomatous mechanism
- Th1 cells secret gamma-IFN to act macros
- TNF-alpha from macro induce and maintain granuloma
anti TNF drugs can sequester granuloma to break down and disseminate disease, test for TB before starting
granulation tissue
characteristics
- prolif of fibroblasts
- new thin walled delicate capillaries bc trying to repair
- fibros and caps are in loose ECM
- scattered macros and other inflamm cells, esp early stage
granulomas
epithelioid cells (aggs of macros) + collar of lymphocytes and plasma cells
surrounding rim of fibroblasts and CT in older ones
fuse to form multinucleated giant cells (langhans type if peripheral ring pattern or foreign body type if haphazard arrangement)
NOT the same as langerhan cells
foreign body granulomas
form in resp to inert foregin bodies like splinters, sutures, breast implant, glass
-will be inside of granuloma since walled off
form when material too large to be phagocytosed
lymphangitis
inflamm of lymphatic channel
leuks and cell debris in lymphatics
-blood poisoning (red streaks up arm) seen
reactive lymphadenitis
inflamm of draining lymph node
may gain access to blood stream if overwhelm LN = bacteremia
systemic effects clinical signs
acute phase response or SIRS
- fever
- change serum acute phase proteins
- inc WBCs
- dec appetite
- altered sleep patterns
systemic effects - fever
inc 1-4 degrees when due to infection
LPS from bacterial product (exogenous pyrogen) stim prod of IL1 and TNF (endogenous pyrogens)
IL1 and TNF = inc COX and PG syn via AA @ hypothalamic thermoreg center aka vascular cells and perivascular
-PGE2 resets body temp
fever effects
improve
acute phase proteins
syn in liver
-CRP
-ceruloplasmin
-haptoglobin
-fibrinogen
-serum amyloid A protein
acute phase proteins mechanisms
syn upreg by IL1,6,TNF-alpha
leukocytosis
inc total WBC count to 15,000-20,000
-normally 4,000-10,000
if >
systemic shift left
inc immature WBC
neutrophilia
inc absolute # of neutros in most bacterial infections
lymphocytosis
inc in absolute # of lymphs in viral infections
-mononucleosis, mumps, german measles/rubella
T cells, B cells, plasma cells
eosinophilia
inc abs # of eosins in asthma, hay fever, parasitic infections
leukopenia
dec absolute # of WBC in typhoid fever, debilitated hosts or overwhelming infection, some viral infectionszxxx
other manifestations of systemic inflamm
- ANS- inc pulse and BP, dec sweating after redirected blood flow from cutaneous to deep vascular beds to min heat loss
- behavioral- shivering, chills, anorexia, somnolence, malaise
sepsis
severe bacterial infections with large # LPS and micro-orgs = large quantity of cytokines esp TNF and IL1
xs cytokines = cardiovasc failure, microthrombi (DIC), liver injury form hypoglycemia
-if all 3 then septic shock
defective inflamm
inc susceptibility to infections + delayed wound healing
excessive inflamm
severe and/or long time inflamm
basis of many diseases esp cancer
-also autoimmune, atherosclerosis, ischemic heart disease, neurodegenerative
longer inflamm persist = inc risk cancer
cancer
ROS and RNS (inflam mediators) can damage cells membrane and proteins
-also DNA breakage and promote deamination of DNA = mutagenic events
