Path (4/5) Acute/chronic Inflammation

Front 1

Define:
INFLAMMATION

Back 1

-a host response
-comprising movement of fluid and leukocytes from the blood to the extra-vascular tissues
-To localize and eliminate material perceived as unwanted

Front 2

Define:
EMIGRATION

Back 2

movement of leukocytes out of the vessels into the tissues

(EXTRAVASATION: laminar flow, stasis, rolling, adhesion, diapedesistransmigration, chemotaxis)

Front 3

Define:
DIAPEDESIS

Back 3

transmigration of cell across endothelium

final step in extravasation of leukocytes, induced by endothelial activation and expression of surface molecules

Front 4

Define:
CHEMOTAXIS

Back 4

locomotion along a chemical gradient
chemoattractants:
-exogenous (target-derived), eg bacterial lipids and peptides
-endogenous (host-derived), eg chemokines (C5a, LTB4, IL-8)

Front 5

Define:
FIBRINOUS INFLAMMATION

Back 5

type of ACUTE INFLAMMATION, characterized by large increase in vascular permeability, allowing fibrinogen to pass vascular barrier, fibrin is formed and deposited forming a fibrinous exudate (e.g. fibrinous pericarditis and meningitis)

Front 6

Define:
EXUDATE vs. TRANSUDATE

Back 6

TRANSUDATE: clear, liquid, spec.grav<1.020, protein < 3.0gm/dl, few cells

EXUDATE: turbid, viscous (pus-like), spec.grav.>1.020, protein>3.0gm/dl, numerous cells (leukocytes) HALLMARK OF ACUTE INFLAMMATION

Front 7

Define:
SUPPURATIVE

Back 7

type of inflammation, neutrophils completely digest tissues and themselves, leaving a collection of puss = ABSCESS

Front 8

Define:
PUS

Back 8

exudate
typical of ACUTE INFLAMATION
protein rich fluid secondary to increased vascular permeability

Front 9

Define:
GRANULATION TISSUE

Back 9

scar tissue, if inflammation is not resolved (restored to normal), this healing tissue replacement is formed by proliferating fibroblasts and vascular endothelial cells

Front 10

Define:
GRANULOMA

Back 10

-a FOCUS of CHRONIC INFLAMMATION consisting of:
-microscopic aggrecation of macrophages, transformed into epithelioid histocytes (sometimes giant cells) surrounded by collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells (body's attempt to wall off undigestable material)

Front 11

ulcer

Back 11

local defect, or excavation of the surface of an organ or tissue that is produced by the sloughing off of INFLAMMATORY NECROTIC TISSUE

can occur only when tissue necrosis and resultant inflammation exist on or near a surface

ACUTE STAGE: intense PMN infiltration and vasodilation
CHRONICITY: marbgins and base develop fibroblastic proliferation, scarring, & accumulation of Lymphocytes, MOs and Plasma cells

Front 12

fibrosis

Back 12

Healing by connective tissue replacement (fibrosis). This occurs after substantial tissue destruction, when the inflammatory injury involves tissues that are incapable of regeneration, or when there is abundant fibrin exudation. When the fibrinous exudate in tissue or serous cavities (pleura, peritoneum) cannot be adequately cleared, connective tissue grows into the area of exudate, converting it into a mass of fibrous tissue-a process also called organization.

Front 13

fibrin

Back 13

an acute phase protein, elevated in inflammation
involved in clot formation, Processes in the coagulation cascade activate the zymogen prothrombin to the serine protease thrombin, which is responsible for converting fibrinogen into fibrin. Fibrin is then cross linked by factor XIII to form a clot.

Front 14

resolution of inflammation

Back 14

restoration of the site of acute inflammation to normal -results when the injury is limited or short-lived or when there has been little tissue destruction and the damaged parenchymal cells can regenerate.
-involves neutralization or spontaneous decay of the chemical mediators, with subsequent return of normal vascular permeability, cessation of leukocytic infiltration, death (largely by apoptosis) of neutrophils, and finally removal of edema fluid and protein, leukocytes, foreign agents, and necrotic debris from the site
-Lymphatics and phagocytes play a role

Front 15

organization following inflammation

Back 15

Conversion of the fibrinous exudate to scar tissue

Front 16

abscess

Back 16

localized collection of purulent inflammatory tissue caused by suppuration buried in a tissue, an organ, or a confined space. They are produced by deep seeding of pyogenic bacteria into a tissue
-have a central region that appears as a mass of necrotic leukocytes and tissue cells.
-usually a zone of preserved neutrophils around this necrotic focus
-outside this region vascular dilation and parenchymal and fibroblastic proliferation occur, indicating the beginning of repair.

Front 17

pyogenic

Back 17

"PUS-PRODUCING"
Certain bacteria (e.g., staphylococci) produce this localized suppuration and are therefore referred to as pyogenic (pus-producing) bacteria. A common example of an acute suppurative inflammation is acute appendicitis.

Front 18

pavementing, describes what part of LEUKOCYTE EXTRAVASATION

Back 18

the endothelial wall of a bloodvessel can be virtually lined by white cells during the adhesion phase just before diapedesis

Front 19

margination, describes what part of LEUKOCYTE EXTRAVASATION

Back 19

accumulation of leukocytes (WBCs) in peripheral position along endothelial surface of vessel lumen

Front 20

resolution of acute inflammation

Back 20

-clearance if injurious stimuli
-clearance of mediators and acute inflammatory cells
-replacement of injured cells
-normal function

Front 21

typical triggers of ACUTE INFLAMMATION

Back 21

-Infections and microbial toxins
-Trauma
-Physical and chemical agents (burns, etc..)
-Tissue Necrosis
-Foreign Bodies
-Immune Rxns

Front 22

typical triggers of CHRONIC INFLAMMATION

Back 22

-Viral infections
-Chronic Infections
-Persistent Injury
-Autoimmune diseases

Front 23

Vascular changes that typify ACUTE INFLAMMATION

Back 23

-VASODILATION
-INCREASED PERMEABILITY of microvasculature
-INCREASED VISCOSITY OF BLOOD
-STASIS

Front 24

Leukocyte subtypes involved in ACUTE INFLAMMATION

Back 24

predominately PMN NEUTROPHILS
some macrophages, few plasma cells and eosinophils plus MORE NEUTROPHILS

Front 25

exudate is a hallmark characteristic of acute or chronic inflammation?

Back 25

HALLMARK OF ACUTE INFLAMMATION!!!

along with PMNs!

Front 26

typical chronic inflammatory response is characterized by:

Back 26

combinations of lymphocytes,
plasma cells and macrophages
infiltrating a tissue in response to a specific stimulus

Front 27

temporal sequence of alterations in blood flow, during response to injury

Back 27

stimulus: HISTAMINE: major inducer of vascular changes
-mediators (esp. histamine, NO) induce vasodilation of arterioles, opening capillaries (+bloodflow/hydrostatic pressure)
-microvascular leakage (-oncotic pressure)
-Increased Viscosity/Stasis
-leukocyte accumulation, eventual transcytosis

Front 28

sequence of events in leukocyte extravasation

Back 28

1. in lumen: margination, rolling, expression of adhesion molecules and adhesion to activated
endothelium
2. transmigration (diapedesis)across endothelium
3. migration in interstitial tissues toward a chemotactic stimulus (chemotaxis)
4. Leukocyte activation
5. Phagocytosis (recognition/attachment, engulfment, killing & degradation)
6. EC release of lysosomal enzymes by leukocytes

Front 29

Once neutrophils reach target of chemotaxis what do they do?

Back 29

PHAGOCYTOSIS

RELEASE OF LYSOSOMAL ENZYMES

Front 30

CARDINAL SIGNS OF INFLAMMATION
4: described by CELCUS

Virchow added one more

Back 30

RUBOR (redness),
TUMOR (swelling),
CALOR (heat),
DOLAR (pain),
Functio Laesa (loss of fxn)

Front 31

carefully orchestrated process involving:
- Soluble mediators
-Vascular responses
-Cellular responses
-Humoral responses

Back 31

Inflammation

Front 32

3 Major events of ACUTE INFLAMMATION

Back 32

1)Hemodynamic changes
2)+ vascular permeability
3) Extravasation of Leukocytes

Front 33

How does Inflammation
start?

Back 33

Stimuli too numerous to list:
Bacteria Dead tissue
Foreign bodies Antibody-complement
Trauma

Front 34

What surrounds splinter in acute inflammatory response?

Back 34

cellulose cavity and EXUDATE = PUS

BLOOD VESSELS, dilated, surrounded by cells (GOING TO BE NEUTROPHILS)

Front 35

HISTAMINE
-source:
-primary role in inflammation:

Back 35

source: MAST CELLS and BASOPHILS

primary role in inflammation:
+ VASCULAR LEAKAGE

Front 36

C3a and C5a are involved in what parts of he inflammatory response?

Back 36

VASCULAR LEAKAGE
CHEMOTAXIS
MACROPHAGE (opsonization)
C5a more powerful chemoattractant than C3a

Front 37

Fibrin is a mediator of what inflammatory processes?

Back 37

VASCULAR LEAKAGE
CHEMOTAXIS of NEUTROPHILS

Front 38

primary role of prostaglandins in inflammation

Back 38

potentiate other mediators (involved in vasodilation, pain, fever)

Front 39

SRS-A
(source:)
(mediates what process?)

Back 39

produced by leukocytes, mast cells

BRONCHOCONSTRICTION

Front 40

TRIPLE RESPONSE OF LEWIS

Back 40

vessel changes in acute inflammation
1) Increased Blood Flow (vasodilation of pre-cap arterioles induced by:
-cell-derived (mast cells: histamine, platelets: serototonin) or
-plasma-derived (complement) VASOACTIVE MEDIATORS
2. Increased permeability of post-cap venules
(a) gaps
(b) transcytosis
(c) unexplained mechanisms
3) Stasis

Front 41

How does opsonization aid in recognition of target material for phagocytosis

Back 41

opsonins (host-derived factors) bind to target
1) Leukocyte "recognizes" and binds opsonin via receptor
2) Opsonin optimizes recognition of particles as "foreign"
3) Helps overcome electrostatic repulsion (negative charges on microbes and on host leukocytes repel one another)

Front 42

OPSONINS:
cell-derived
plasma-derived

Back 42

cell-derived: Fc portion of IgG binds FcgR on leukocyte

plasma-derived:
1)C3b/C3bi bind CR1, CR2, CR3 on leukocyte
2) Carbohydrate-binding proteins/collectins bind C1q receptor on leukocyte

Front 43

Phagocytosis (engulfmant of target material) involves:

Back 43

a) pseudopodia engulf material to form PHAGOSOME
b) lysosomal granules fuse with phagosome to form PHAGOLYSOSOME

Front 44

Destruction of target material by Leukocyte
a) Oxygen dependent

Back 44

a) O2 dpdt:
(1) NADPH oxidase: --> 2O2-
2) 2O2- + 2H+ --> H2O2 + O2
3) Myeloperoxidase converts H2O2 to HOCl

Front 45

Destruction of target material by Leukocyte
a) Oxygen independent

Back 45

1) BPI (bactericidal permeability increasing protein)
2) Lysozyme
3) Lactoferrin
4) Major basic protein
5) Defensin

Front 46

most chronic inflammation reactions are what type of immune reactions?

Back 46

humoral
cellular
or BOTH

Front 47

chronic inflammation involves predominantly what cell types?

Back 47

lymphocytes (CD4 and CD8) and macrophages

Front 48

Examles of CHRONIC INFLAMMATION

Back 48

1. Predominantly lymphocytes:
(a) Chronic (HASHIMOTO'S) thyroiditis
(b) RA
2. GRANULOMA
(a) foreign body rxn
(b) hypersensitivity granuloma

Front 49

reactions involved in Chronic thyroiditis

(gross appearance)

Back 49

Type II (Ab-mediated cytotoxicity) and Type IV (DTH) reactions


HYPOTHYROIDISM, GOITER with possible compression of trachea

Front 50

histological characteristics of RA chronic inflammation

Back 50

involves VILLOUS SYNOVITIS:
villous projections with many lymphocytes and plama cells

Front 51

histo of FOREIGN BODY REACTION granuloma

Back 51

inert foreign material, surrounded by activates MOs, may fuse to form multinucleate giant cells

mild fibrous reaction may occur

Front 52

histo of Hypersensitivity granuloma

Back 52

-circumscribed collection of epithelioid cells
-lymphocyes always persent
-may or may not also include multinucleate giant cells, necrosis, surrounding fibrosis

Front 53

outcome of hypersensitivity granuloma

Back 53

early granulomas may go on to resolution,

most granulomas lead to at least some fibrosis and scarring

Front 54

SCAR

Back 54

alternate tissue laid down as part of "healing," when regeneration of original tissue is not possible due to ECM damage

Front 55

KELOID

Back 55

if the scar tissue grows beyond the boundaries of the original wound and does not regress, it is called a keloid.
-more common in African- Americans
-mechanisms of keloid formation are unknown.

Front 56

hypertrophic scar

Back 56

The accumulation of excessive amounts of collagen may give rise to a raised scar known as a hypertrophic scar;

Front 57

KELOID

Back 57

What part of sequelae of inflammation is depicted here?

Front 58

Potential Sequelae of ACUTE Inflammation

Back 58

*Resolution (RARE)
*Chronic Inflammation
*Abscess Formation
*Fibrosis (SCAR)
*Effusion
*Serositis (purulent or fibrinous)
*Necrosis
*Chronic Inflammation

Front 59

Potential Sequelae of CHRONIC Inflammation

Back 59

*Tissue Necrosis
*Joint Destruction
*Autoamputation (leprosy) *Severe tissue scarring (TB)
*Amyloid Deposition
*Neurological problems

Front 60

What does resolution of inflammation entail?

Back 60

RETURN TO NORMAL:
no more calor, rubor, dolor, tumor or functio laesa
(example, poison ivy vesicles, zoster lesions- BM remains INTACT!)

Front 61

why do smallpox lesions not resolve?

Back 61

Lesions cause tissue necrosis right down through dermis, BM destroyed, tissue dissolved (resulting in SCARRING)

Front 62

deletorious effects of scarring:

Back 62

*Scar tissue has no function other than binding together damaged sittue elements.
*can obstruct, block, constrict normal tissue
*can entrap normal tissues or structures thus diminishing or destroying their function
*Over time scar tissue constricts/tightens structures
*Scar tissue can bind-together structures that should remain independent (adhesions)

Front 63

volvulus

Back 63

loop of bowel twisted off due to adhesion (estrangulated, ischemic, infarcted)

Front 64

Histopathological definition of CHRONIC inflammation, characterized by what cell types?

Back 64

lymphocytes, plasma cells and macrophages predominate

Front 65

How does Staphylococcus aureus (ACUTE INFLAMMATION) become chronic in AIDS patient?

Back 65

in this situation what should be an “acute” inflammatory process has become “chronic” because patient can’t RESOLVE (has lost even ability for neutrophils to function appropriately, not opsonizing bacteria for neutrophil engulfment

Front 66

CHRONIC INFLAMMATION usually results in:

Back 66

SCAR
or TISSUE DEATH

Front 67

What is found inside RA nodules?

Back 67

necrotic tissue

Front 68

What is found in the center of a TB GRANULOMA (of lung)?

Back 68

CASEOUS NECROSIS

Front 69

Fistula

Back 69

NON anatomic tube (forms in healing response instead of scar)

Front 70

Inflammation in RA joints stimulates formation of these on synovial surface:

Back 70

stimulates PROLIFERATION of CELLS forming VILLI on Synovial surface

Front 71

Amyloidosis

Back 71

deposition of insoluble proteins diffusely in tissues, replacing normal tissues (INFLAMMATION CAN BE ELSEWHERE IN BODY)
examples: TB, leprosy

Front 72

How can chronic inflammation result in seizures or hydrocephaly?

Back 72

inflammation of surface of brain can produce glial scars (astrocytic gliosis = eleptogenic)

Front 73

abscess as sequelae of ACUTE INFLAMMATION involves complete

Back 73

complete digestion of existing material by neutrophils, including neutrophils digesting themselves

Front 74

contracture

Back 74

develops when the normally elastic tissues are replaced by fibrous tissue. prevents normal movement.

Contractures occur primarily in the skin, underlying tissues, muscle, tendons, and joint areas.