Cardinal signs of inflammation (4)
Rubor - redness
Tumor - swelling
Callor - increased temperature
Dollor - pain
functiolaesa added by Greeks, loss of function
What are the stages of acute inflammation?
1) vascular stage
2) cellular stage
3) inflammatory mediators
4) acute phase response
Describe 1st stage of inflammation
Vascular stage
1) transient vasoconstriction (a few seconds)
2) followed by vasodilation --> opening of capillary beds, increasing permeability
3) vasodilation creates redness erythema (rubor)
4) increased warmth (callor)
5) protein-rich exudate --> stagn
Describe the cells involved in stage 2 of inflammation
Cellular stage
1) neutrophils (1st on the scene) come in mass, armed w/ enzymes to destroy bacteria and break down dead tissue. neutrophil rxn - fast and widespread --> body calls for more neutrophils, so it dumps immature neutrophils out (called BAND CEL
What does the presence of band cells indicates?
widespread infection
Band cells = immature neutrophils
What are the steps in the cellular phase of inflammation?
Stage 2 -
1) Margination + Adhesion - neutrophils move to parameter/margin of vessel, adhere to vessel wall
2) Transmigration/Extravasation - "degress" - neutrophils leaving vessel
3) Chemotaxis - macrophages/neutrophils are following a trail, acting like
Vessels are fenestrated. What does this mean? Why is this important?
Fenestrated - cell sends out pseudopod and pulls itself out of vessel by using this pseudopod as an anchor
What are the three stages of phagocytosis? Describe these stages
1) Recognition and Adherence - recognition of bacteria that the macrophage has been tracking. adheres to the pseudopodia
2) Engulfment - other pseudopodia comes out, gives bacteria a hug, pseudopodia fuse and engulf it. now bacteria is INTRACELLULAR
3) In
Where are inflammatory mediators derived from?
Inflammatory mediators are derived in the PLASMA or various types of CELLS
Plasma-derived mediators are manufactured where?
LIVER
Name the plasma-derived mediators (3)
Acute phase proteins
Factor XII
Complement proteins
Acute phase proteins result in
Acute phase proteins result in FEVER and INFLAMMATION
Factor XII is involved with ___________ and the _________ system
Factor XII (Hageman Factor) activation of the CLOTTING fibrinolytic system and KININ system (BRADYKININ)
Purpose of bradykinin
Bradykinin increases vascular permeability
Functions of the complement system (3)
Complement system:
1) vasodilation
2) increase vascular permeability
3) enhancing phagocytic activity
Name the Cell-derived pre-formed mediators (3)
Cell-derived preformed mediators:
Mast cell- secretes HISTAMINE (vasodilation and inc permeability)
Platelets- kick off SEROTONIN (causes vasoconstriction)
Neutrophils/Macrophages- lysosomal enzymes during the engulfment stage
Name some Cell-derived newly synthesized mediators?
Leukocytes
- prostaglandins
- leukotrienes
- platelet-activating factor
Leukocytes/Macrophages
- nitric oxide
- oxygen derived free radicals
Macrophages/Lymphocytes/Endothelial cells
- cytokines
Effects of nitric oxide as a newly synthesized mediator
Nitric Oxide
- smooth muscle relaxation - vasodilation
- antagonistic to platelets
- oxygen derived free radical - kills infection
Function of cytokines
Cytokines are released by macrophages either to recruit macrophages or cause cells to have other types of behaviors --> including enhancing inflammatory response
What is the Arachidonic cycle?
Archidonic acid is released from injured cell membrane - give off inflammatory mediators.
Corticosteroids SHUT OFF the formation of arachidonic acid and shuts down both pathways
What are the two main pathways triggered by arachidonic acid?
Lipoxygenase pathway
Cyclooxygenase pathway
What mediator is derived from the lipoxygenase pathway?
LEUKOTRIENES
What are the effects of leukotrienes (3)
cause SMOOTH MUSCLE CONTRACTION
pulmonary airway constriction
increases microvascular permeability
What two mediators are derived from the cyclooxygenase pathway?
PROSTAGLANDINS
THROMBOXANE
What are the effects of prostaglandins (2)
induces VASODILATION and BRONCHOCONSTRICTION
inhibits inflammatory cell function
What are the effects of thromboxane A2 (3)
VASOCONSTRICTION
BRONCHOCONSTRICTION
promotes platelet function
Why do corticosteroids work so well?
SHUTS OFF the formation of arachidonic acid, which prevents the lipooxygenase and cyclooxygenase pathways from being activated
What is the role of ASA and NSAIDs in the cyclooxygenase pathway?
ASA and NSAIDs limit the amount of prostaglandins and thrombaxane that is released
Two types of chronic inflammation
Nonspecific Chronic inflammation
Granulomatous inflammation
chronic inflammation can be described as ________-_____________ and can last weeks, months, years
SELF-PERPETUATING
Describe nonspecific chronic inflammation
1) diffuse accumulation of MACROPHAGES and LYMPHOCYTES at the site of injury
2) leads to scar formation by FIBROBLASTS proliferation at inflamed site - trying to wall off cause of inflammation
________________ are present in chronic inflammation but not acute.
Fibroblasts - which WALL OFF inflamed/infectious area
acute inflammation - predominant cell is ______________
acute inflammation, the predominant cell is NEUTROPHILS
chronic inflammation - greater number of ____________ compared to acute inflammation
chronic inflammation, there is a greater number of MACROPHAGES compared to acute inflammation
Describe Granulomatous inflammation
- distinctive form of chronic inflammation, assoc with FOREIGN BODIES
- for one reason or another, the macrophage can't take out the invader, so a GRANULOMA is formed
- 1-2mm in diameter
- mass of MACROPHAGES and LYMPHOCYTES - attempt to wall off of conta
Foreign bodies that may cause a Granulomatous inflammation
splinters
sutures
silica
microorganisms that cause TB
syphillis
sarcoidosis
deep fungal infections
brucellosis
Describe the formation of a Granuloma. Which type of inflammation is this present in?
Chronic inflammation
1) macrophage cannot kill whatever the invader is
2) mass around it - take on epithelioid characteristics
3) coalesce/fuse --> create FOREIGN BODY GIANTS
Local manifestations of inflammation
1) production of exudates
2) abscess
3) ulceration
Production of exudates is typically associated with which type of acute/chronic inflammation?
ACUTE inflammation
serous exudate
- clear/watery b/c low in protein
hemorrhagic exudate
fibrinous exudate
- large amounts of fibrin
membranous exudate
- form on mucous membrane, consist of necrotic cells, that mesh of fibropurulent
purulent/suppurative ex
What is an abscess?
Abscess
- localized area of inflammation containing purulent exudate
- typically consists of NECROTIC CORE surrounded by neutrophils - walled off by FIBROBLASTs
Systemic manifestations of an abscess formation
Inflammation - capillary dilation, fluid exudation, neutrophil migration
Suppuration - development of purulent exudate/tissue debris
Abscess formation - WALLING OFF of the area of purulent (pus) exudate to form an abscess
Systemic manifestations of Inflammation
1) Acute-Phase Response
- HALLMARK: presence of FIBRINOGEN + C-REACTIVE protein
2) White Blood Cell Response
- leukocytosis (inc in WBCs)/assoc leukopenia (dec neutrophils)
3) Lymphadenitis (swelling of lymph nodes)
- PAINFUL PALPABLE lymph nodes - assoc
Describe Acute Phase Response of the systemic manifestation of inflammation
1) release of interleukins, and tumor necrosis factor ALPHA results in skeletal muscle metabolism.
2) breakdown of skeletal muscle leads to a negative nitrogen balance.
3) an increase in ESR, increased # of WBCs, leading to fever
most obvious sign of systemic inflammation
FEVER
Which proteins are created during the Acute-Phase Response of inflammation? What do these proteins do?
Where are these proteins made?
1) FIBRINOGEN - clumping of RBCs - clot. if put in test tube, they SINK --> increased ESR
2) C-REACTIVE PROTEIN - binds to surface of pathogen, targets the pathogen for destruction. ENHANCES PHAGOCYTOSIS
- made in the LIVER
White Blood Cell Response with systemic manifestations of inflammation
1) leukocytosis - bands --> immature WBCs
2) leukopenia - viral infection --> decreased neutrophils. could have used all the neutrophils up