22: Chronic Inflammation 1

duration of chronic inflammation

weeks-years

what are the main cells involved in chronic inflammation?

MACROPHAGES, lymphocytes, plasma cells, and antigen

what characterizes chronic inflammation?

FIBROSIS

what is the connective tissue used in fibrosis?

collagen

what causes granulation tissue formation?

desmoplasia, +/- fibroplasia, neovascularization

true or false: granulation tissue formation is a NORMAL PART OF HEALING

TRUE

causes of chronic inflammation

persistent infections, HS diseases, autoimmune diseases, prolonged exposure to toxin, isolation, defects in leuk formation

what is the SIGNATURE CELL of chronic inflammation?

MONOCYTES/MACROPHAGES

where do monocytes live?

bone marrow and spleen

what cell is this?

macrophage

when do macrophages form?

in response to foreign bodies or persistent ITC pathogens

describe epithelioid macrophages

larger, polygonal shape, can look like epithelial cells

what cell is this?

epithelioid macrophage

describe multinucleated giant cell

2+ macrophages form one large cell

what cells are these?

multinucleated giant cells

where are dendritic cells stored in larger amounts?

skin, mucosal surfaces of resp/GI tracts

unique feature of dendrites

have filipodia (arm)

pathway of dendritic cell

migrates to antigen -> phagocytize -> migrate to lymph organ -> presents to T/B cells

main function of dendritic cells

antigen presentation

what form of immunity do dendritic cells stimulate?

ADAPTIVE

what do lymphocytes play a key role in?

chronic inflammation

how long does it take lymphocytes to enter an area with UNRESOLVED inflammation?

24-48 hrs

what do lymphocytes surround?

granulomas and blood vessels

what do B lymphs differentiate into?

plasma cells

what do plasma cells do?

secrete Igs (antibodies)

different types of antibody

IgA/D/E/G/M

what do the Igs do?

bind/opsonize antigens, marking them for phagocytosis

where are plasma cells located?

bone marrow, lymph nodes, MMs, wound sites

true or false: plasma cells predominate in certain chronic conditions

TRUE

what do fibroblasts do?

produce collagen and EXCM proteins (important for healing)

what cytokine plays a MAJOR ROLE in fibroblast activity/collagen depositiion?

TGF-B

in what species are fibroblasts VERY RESPONSIVE to injury?

CATS

what cells are these?

fibroblasts

4 phases of wound repair

1. hemostasis 2. inflammation 3. proliferation 4. remodeling

what happens during first intention healing?

edges of NON-SEPTIC wound in close proximity to each other (suturing/bandaging ok)

outcome of first intention healing

little trace of wound over time, tensile strength almost the same

what happens during second intention healing?

cut edges too far apart, delays re-epithelization

what is the outcome of second intention healing?

ulcer or fibrin scar that is DIVITED and MUCH WEAKER tissue

describe repair if the BM is DAMAGED

takes longer bc have to remake BM

what is being shown here?

basement membrane (BM)

HIF

hypoxia inducible factor

what does HIF do?

promotes angiogenesis and stimulates cell proliferation

what is angiogenesis?

creation of new blood vessels

new BVs are fragile and not as strong as the original vessels. what does this entail?

increased vascular permeability

most important/potent cell mediator in angiogenesis

VEGF-a

what does VEGF-a do?

stimulates endothelial cell proliferation

what is the counter mechanism that stops angiogenesis?

angiostatin

antigen is sequestered. what is formed?

granuloma or abscess

collagen is layed down. what is occuring?

fibrosis

what causes pus to form?

liquification of affected tissue

what cells/enzymes are used in abscess formation and WHAT DO THEY DO?

myeloperoxidase from neutrophils, liquifies/necroses tissue

what species LACK myeloperoxidase?

birds/reptiles (remember their abscesses are dry/crumbly bc of this)

inner surface of abscess

granulation tissue

outer wall of abscess

collagen

how long does it take to form an abscess?

weeks (so always chronic)

2 types of abscess formation

septic and sterile

true or false: color of exudate from abscess can sometimes tell us type of bacteria present

TRUE

what is a fistula?

track made to drain pus from abscess

phlegmon

no capsule, inflammation spreads along tissue plane

empyema

no capsule, pus accumulates in pre-existing space

granulomatous inflammation

diffuse sheets/spread out inflammation, tissues is overtaken by macrophages

what is this showing?

granulomatous inflammation

granuloma

mass of nodule cells (can be seen grossly)

major cell types in granulomas/matous inflammation

MACROPHAGES

mediator of granulomas

TH1

mediator of granulomatous inflammation

TH2

what is this showing?

granulomas (can see distinctly)

gross apperance of nodular (TH1) granulomas

gray/white, round/oval, firm/hard

what cell types are heavily seen in nodular granulomas?

macrophages, surrounded by fibroblasts/lymphs/plasma cells

caseating granuloma

cheese like appearance

non-caseating granuloma

lacks central necrosis, contains inflammatory cells

gross apperance of diffus (TH2) granulomas

gray/white, poorly demarcated from nearby tisse, firm

what species and organ is most commonly affected by diffuse (TH2) granulomas?

CATTLE and ILEUM

what is this showing?

diffuse (Th2) granuloma

what is this showing?

diffuse (TH2) granuloma histology

gross apperance of granulation tissue

granular appearance, firm

describe arrangment of granulation tissue

fibroblasts PARALLEL to wound, capillaries PERPENDICULAR to wound

what is this showing?

granulation tissue

proud flesh

when granulation tissue becomes excessive/mass like

what is this showing?

proud flesh

scirrhous rxn

contraction of CT that tenses the surrounding tissue, can be restrictive/cause dysfunction!

what does scirrhous rxn looks like?

stress ball with the netting around it

gross apperance of scirrhous rxn

organ smaller + firm, looks like squeezed net stress ball

what is this showing?

scirrhous rxn

re-epithelialization

when epithelial cells at periphery proliferate

what is re-epithelialization VERY RAPID in?

1ST INTENTION HEALING

true or false: in re-epithelialization, cells must move ALONG A BASEMENT MEMBRANE

TRUE (will otherwise result in ulcer)

what is this showing?

ulceration on histology

what is this showing?

re-epithelialization on histology