Acute Inflammation
9/14/2010 6:36:00 PM
Acute Inflammation (AI) y
Signs
for Infection:
o
ubor R ubor
(R edness) edness)
o
Calor
o
Tumor
(Heat) (Swelling)
**all 3 are histamine mediated to cause vasodilation except that ubor R ubor
and
Calor
are arterioles and Tumor increases permeability
of venules of venules to let fluid in interstitial space (edema) o
Dolar
Caused
o y
Loss
(pain) by PGE2 and bradykinin
of Function
Causes: o
Infection, Immune
eactions, R eactions,
Necrosis, trauma, radiation,
burns, punctures Steps:
Vascular
y
Vasoconstriction (few seconds)
y
Vasodilation of arterioles o
Increases blood flow and hydrostatic pressure Histamine, NO, PGI2, serotonin
y
Increase Permeability of Venules o
Endothelial cells contract together to leave gaps Leaks
o
Caused
y
Swelling
y
educed R educed o
out fluid?
by Histamine,
Serotonin, C3a, C5a, LTC4-D4-E4
Blood Flow
Decrease
in hydrostatic pressure by outflo w of fluid into
interstital tissue Steps: Cellular y
NEUTROPHILS o
y
aggregate, neutrophils in periphery
E-Selectin o
y
R BC
primary leukocytes in acute inflammation
makes neutophils roll along endothelium
Deficiency
in selectin
LAD
2
Adhesion o
Half the neutrophils are in circulating pool, half are in marginal pool
Beta2
Intergrins (CD11a:CD18) help
with
adhesion
Deficiency
y
in
CD11a:CD18 LAD
type 1
Activated by C5a and leukotriene
B4
(LTB4) Enhanced by endotoxins
o
(neutropenia) y
Inactivated by Catecholamines, corticosteroids and lithium
ICAM and VCAM binds to integrin on surface of neutofiles Mediated by Interleukin 1 and
Tumor Necrosis
Factor **neutrophils important in umbilical cord seperation o
If umbilical cord does not come off by a month then its problem Also severe gingivitis and poor
wound
healing means no
neutrophils y
Diapedesis o
Neutrophils rolls along the endothelium and dissolves thru to enter the interstial fluid
It helps dilute the bacterial toxin and provins IgG and C3b to help with phagocytosis
y
Chemostasis o
y
helps neutrophil find infection
Mediators
C5a
and
LTB4
and Interluekin 8
Phagocytosis o
Opsonization
Opsonin (IgG & C3b) attach to bacteria
Neutrophil attaches to bacteria *Bruton¶s agammaglobulinema Is a opsonization defect
o
Ingestion
Neutrophils engulf bacteria into vacuoles
Lysosomes
empty hydrolytic enzymes into
vacuoles producing phagolysosomes *Chediak
Higashi
phagolysosomes o
Killing
sydrome cannot produce
MPO (O2 dependent myeloperoxidase)
Only
in
neutrophils and monocytes (not macrophages)
Produces superoxide O2y
NADPH oxidase converts oxygen to superoxide o
R eleases
Superoxide
respiratory burst
dismutase converts superoxide to
hydrogen peroxide
MPO combines HOCL-
with
H2O2 and
Chloride
to make
kills bacteria
**Chronic Granulomatous Disease
X Linked
**MPO
or AutoR ecessive
y
Deficiency of NADPH oxidase
y
No O2- and H2O2 produced
y
No respiratory burst
Deficiency
AutoR ecessive y
O2- and H2O2 produced
y
There
is a respiratory burst
**G6PDH defiency
no NADPH Oxidase
**Diabetes Mellitus
TYPES y
Defects
in phagocytosis and chemotaxis
OF AI Purulent (suppurative) inflammation o
Proliferation of pus forming organisms
S.
Aureus (most common cause
Contains y
coagulase
Cleves o
y
fibrinogen to fibrin (blood
Traps
Clots)
bacteria
Fibrinous Inflammation o
Due to increased vessel permeability with deposition of fibrin
y
Serous o
Often occurs on pericardium, peritoneum and pleura
Inflammation
Thin
Watery Exudate
Insuffinct amount of fibrinogen to produce fibrin
y
Examples blisters
Pseudomembranous Inflammation o
Bacterial toxin (clostridium difficle) causes damaged to mucousal lining
pseudomembranous colitis
Produces shaggy membrane composed of necrotic tissue
IMMUNOGLOBIN M Transudate y
Can
clear fluid, protein less produce pitting edema
Exudate ±> protein full, cell rich (neutrophil) y
Produces swelling of tissue but no pitting edma o
Ex pus
Fever Occurs Acte Phase y
R eaction
mediated by IL6
Endocirne ± secretion of C
R eactive
protein,
Associated Protein y
Autonomic ± Increased pulse and BP
y
Behavorial ± chills, rigor,anorexia, malaise
Bacterial infection Parasite Viral
neutrophilia
eosinophilia
lymphocytosis
Serum
Amyloid
Cell
Mediators
9/14/2010 6:36:00 PM
Vasodilation y
Histamine, nitric oxide, PGI2, serotonin
Vasoconstriction y
Thromboxane
A2
Increased Vessel Permeability y
Histamine, bradykinin,
y
Bradykinin, PGE2
y
PGE2, IL1, TNF, IL6
LTC4-D4-E4, C3a
& C5a,
Serotonin
Pain Fever Chemotaxis y
C5a, LTB4,
IL8, IgG
Prostatagladins comes from macrophages, endothelial cells, and platelets and
COX y
Makes o
TXA2
TXA2
via PGH2 helps
with
clotting
Leukotrines y
Comes
from Aracadoninc Acid via lipoxygenase mediated
hydroxylation o
Inhibited by zileuton
Bradykinin y
Product of kinin system activated by activated Factor 12
Chemokines y
Activates neutrophil chemotaxis o
Comes
from endothelial cells
Complement y
Syn
from liver
o
C3a,C5as
and so on
o
Increase vascular permeability
o
Stimulates
mast cells
Interluekins y
Comes
from macrophages, moncytes, dendritic cells and endothelial
cells o
IL1
Fever, Leukocyte adhenion, coagulation
Histamine y
Comes
from mast cells
Nitric Oxide y
Comes
from macrophages, platelets and enterochromaffin cells,
endothelial cells Serotonin y
Comes
from platelets, mast cells
y
Increases vascular permeability
Chronic
Inflammation
9/14/2010 6:36:00 PM
Inflammation that is prolonged y
Causes: o
Infections ex.
Hep
C
Most common
y
TB, Leprosy,
o
Autoimmune
o
Sterile
R heumatic
Agents
Silica,
Arth.
Systemic Lupus
Uric Acid,
Silicone
in breast implants
Morphology o
Cell
involved
Monoctyes
Macrophages (key cells)
Lymphocytes
Plasma
Eosinophils
o
Necrosis
o
Destruction of Parenchyma
o
Loss
not as prominent
of tissue function
repaired via fibrosis
Formation of Granulation Tissue (Scar Tissue)
Needs Fibronectin
Fibroblast makes the collagen on the bv to help form new blood vessels Needs
y
Vascular Endothelial
Growth
Factor (VEGF) and Fibroblast Growth Factor (FGF) o
Important for angiogenesis
Increase in serum IgG y
Granuloma inflammation o
Aggregates of modified macrophages
Surrounded
o
Immune Granuloma (TB)
Non caseating
Central
o
May have central area of caseation in
Based on pathogenesis
o
by lymphocytes and fibrosis
Mechanism
area has not gone under necrosis,
See
giant cells and lymphocytes
TB
CD4
cells activated and produce IFN Gamma IFN Gamma acts on macrophage and macrophage becomes epitheloid cell and becomes a
wall
R epair
9/14/2010 6:36:00 PM
Tissue R epair: y
Two
Factors
o
Parenchymal
o
R epair
Parenchymal y
Cell
Depends o
by
Cell R egeneration
Connective
tissue
R egeneration
on
Labile
Cell
ability to reproduce
(stem) and
Stable
(don¶t replicate unless needed)
(fibroblast, hepatocytes, kidney cells) can replicate o
Permanent (cardiac, and striated muscle) are replaced by scar tissue
o
Cell Cycle
G1 is the most variable phase in cell cycle
Controlled y
by
and
Cyclin D
Cyclin d binds to Cdk4 causing the cell to enter
Cdk4
R epressed
S
by
phase R etinoblastoma
y
Keeps
y
Cdk4 binds to
(R B)
cell in G1 phase R B
to allow cell to go into
S
phase
TP53 y
Inhibits
y
Make sure that o
Cdk4 DNA
damaged is repaired
If damage is too much BAX is activated
Inhibits BCL2 (antiapotosis)
R elease
cytochome c and
apotosis occurs o
R estoration
and R epair
needs preservation of basement membrane
ECM
by connective tissue
**macrophages play major role in healing process y
Occurs
y
Steps o
when
injury is severe or persistant
in repair R equires
neutrophil transmigration to liquefy injury tissue and
macrophages to remove the debris o
R equires
formation of granulation tissue
o
Accumatulates in ECM and produces scar
Needs
Type
3
Collagen
(major component of connective
tissue) o
Collagen Synthesis
First intention: clean
wound,
edges are close together, less time to heal, less
fibrosis, epithelila regereration occurs Second
intention: big defect, edges are messed up
Factors that impair y
Persistant infection o
Most common cause of impaired
y
Healing
Staph
Aureus
wound
healing
most common pathogen
Metabolic disorders o
Ex.
Diabetes
Mellitus
Causes
decreased blood flow and increase glucose in
tissue y
Nutrition defiencies o
Protein
o
Vit
o
Copper
C Scurvy
causes Ehlers
Stretchy
o
Danlos
skin
Cant
make cross links
Zinc
Needed for removal and remodeling by activating metalloproteinase, degrades excess extracellular matrix
o
Glucocorticoids
Interferes
with
collagen formation, prevents healing
process
R epair y
Used to prevent over scarring ( Keloids)
in other tissue Liver o
Mild Injury (Hep A)
R egeneration
o
Severe
of hepatoctyes
Will restore to normal if cytoskeleton is intact
Injury (Hep
C)
Increased fibrosis
will
occur and lead to cirrhosis
R egenerative
nodules that develop lack sinusoids
and portal triad y
Lung o
Type
2 Pneuoctyes repair the cell Synthesizes
y
Astroctyes and Microglial cells
Periphreal Nerve o
y
Schwann Cells
Heart o
Cardiac
Keloid y
occurs if type 2 is damaged to much
Brain o
y
R DS
surfactant
muscle is permanent
R eplaced
by scar tissue
usually in African Americans Excess of synthesis of type 3 collagen
Proud Flesh y
Excessive granulation tissue o
May block epithelial regeenreation
Hypertrophic scarring y
Type
1 collagen
Contracture y
Permanent tighting of skin, muscle, tendon, ligaments and prevents normal body movment
