Acute Inflammation and Healing - Latham Flashcards
What are the four steps of the vascular response?
- smooth muscle relaxation in arteries and arterioles to allow blood to rush in
- vascular dilation = hyperemia (blood moving fast)
- endothelial cells contract creating intracellular gaps
- increased vascular permeability = first water and salt leak out including fibrinogen and immunoglobulins
What is transudate?
extravascular fluid that is low in protein at first when the intracellular gaps are small
What is exudate?
when large mols like fibrinogen and immunoglobulins leak out
= inflammatory edema
What is phase I of acute inflammation?
vascular response
What is phase II of acute inflammation?
- marginate and roll
- adhere to EC
- transmigrate through EC gaps
- move to site of injury along chemoattract gradient
neutrophils
PMNs - major effector cells of acute inflammation
What does congestion lead to?
decreased blood flow and stasis as edema increases which leads to a loss of laminar flow
What do chemoattractants and integrins allow for?
allows neutrophils to squeeze out through endothelial gaps
- can break through the basement membrane and move into the extravascular matrix
selectins
platelets, leukocytes, and endothelial cells express selectins
- bind to glycoprotein receptor
- rolling
integrins
adherence, migration
- tighter binding
- can bind to PECAM (platelet endothelial cell adhesion molecule)
What is the first responder cell
neutrophil
What is the second responder cell
monocytes - move into the tissues by same mechanism as neutrophil
What attracts monocytes
- cells bind to fibrin matrix and move toward an increasing chemotaxis concentration
What are exogenous signals?
bacterial products - LPS
- PAMPs
DAMPs
endogenous signals
Endogenous signals
necrotic cells and fibrinopeptides
- complement - produces byproducts along the way
- leukotriene
- chemoattractant factors
- tells responding cells where to go
Complement 5a
a very good chemoattractant
LTB4
a product of the AA breakdown
- chemoattractant
IL-8
chemokine for neutrophils
MCP-1
monocyte chemoattractant
Where are mast cells found
connective tissue all over the body
Which two cell types contain preformed histamine
mast cells and platelets
What do trauma and burns stimulate?
mast cells and platelets to have immediately release of preformed histamine
What is the major player in the acute inflammatory response in the first 20-30 minutes?
histamine
what is the maintenance of vascular tone dependent on
nitric oxide
- released from stimulated endothelial cells to affect smooth muscle relaxation
What macrophages use NO for?
to produce antimicrobial free radicals
- cells contain inducible NO
- which can metabolize arginine
prostaglandins
vasoactive properties
- systemic signs of infection = fever pain
What produces LTB4
leukotrienes produce LTB4 as a chemoattractant to neutrophils
Which cytokines activate macrophages and induce selections?
TNF alpha, IL-1
Which cytokine is responsible for fever?
IL-1
Which cytokine acts as a chemotaxis for PMNs
IL-8
bradykinin
- production of pain
C5a
chemotaxin
- vasoactive
c3b
oxidant
why do we ice
constrict the vessels and decrease blood flow and alleviate some pain
neutrophil phagocytosis
- rich in myeloperoxidase
- antibody coats particle and binds to receptor for antibodies on the neutrophil (Fc receptor) to help the neutrophil to engage
- factor C3 coats particulate matter
opsonin
coat the particulate matter to engulf by phagocytosis to enhance phagocytosis
- antibody or C3
Do neutrophils require oxygen?
no, but it can do an even better job with oxygen
- with oxygen it can take NADPH and oxidize it will allow it to reduce oxygen to create free radicals to kill whatever is ingested
Myeloperoxidase
neutrophil has these in abundance
- myloperoxidase can produce OCl- free radical
What does neutrophil tissue infiltration tell us
acute inflammation
- first responders to injury
What do macrophages tell us
what monocytes become as they move into the issues
- increase after 24-28 and become predominant cell type
What is inflammatory edema
fluid exudate, protein rich
purulent suppurative
pus = cell rich
fibrinous exudate
exudate that is rich in fibrin
mucinous exudate
exudate that is rich inmucin
sanginous exudate
hemorrhagic, common with necrosis
What would meningitis in the brain show
suppurative exudate
- pus between the gyri
abscess
liquefactive necrosis of tissue surrounded by normal tissue
- suppurative exudate
- rich in neutrophils
ulcer
liquifactive necrosis at tissue surface
- suppurative exudate
- on the surface of the mucosa
leukocytosis
increased release of neutrophils from marrow
- systemic sign of acute inflammation
What does a release of IL-1 cause
leukocytosis
- increased release of neutrophils from marrow
What is released into systemic circulation during a fever?
prostaglandin and IL-1
- affect thermoregulation on hypothalamus and pulse rate
What do IL-6 and IL-1 stimulate the liver to produce?
acute phase proteins = CRP
- bind to dead cells and pathogens and activates complement cascade
What do elevated levels of CRP indicate?
active levels of inflammation
- could be sign of heart attack
erythrocyte sedimentation rate
ESR
- IL-6 and IL-1 increase liver synthesis of fibrinogen which leads to increased RBC aggregation –> sediment
What are DAMPs chemoattractants to?
neutrophils
Which cell is the key effect cell for healing
macrophage
- produce EGG, VGF, GFG, TGFalpha (promote cell growth)
- fibrogenesis
- metallaproteinases (wound remodeling)
what are the 4 steps for healing and repair?
- removal of edema and debris
- regeneration of native tissues - need activate macrophages to make all the growth factors
- organization - proliferation of 3 major cell types
- fibrosis - scar
What reabsorb edema during healing?
lymphatics
Which cells remove cell and tissue debris during healing?
macrophages
granulation tissue
the term that is used for wound healing, provisional tissue that is laid down
- contains macrophages that release growth factors
- endothelial cells - angiogenesis
- fibroblasts to make collagen
fibrosis/scar formation
macrophages recognize fibrovascular granulation tissue
- fibroblasts contract to close the wound and synthesize collage to create strength within the scar
- mature scar has few cells and little vascular support
During mid-late wound organization which factors are important?
TGFbeta, FGF, PDGF
- stimulate fibroblast proliferation/motility, collagen, fibronectin synthesis
healing by first intention
- stitching to bring the wound close together
- decrease the amount of time for healing
- decrease the provisional tissues that are necessary
- pretty good union by two weeks
healing by second intention
- although you can bring in new epidermal cells but the tissue underneath may not be so good at replication
- left with scar that can be seen or may be present under the skin
keloid
- production of excess collagen for wound healing
- excessive scar production
- keloid overlaps with normal skin
What are the key cells in chronic inflammation
macrophages and lymphocytes are the key cells
When does CT proliferation occur in acute inflammation
as inflammation subsides
When does CT proliferation occur in chronic inflammation
with ongoing inflammation
