Chronic Inflammation pdf - د. فائزة

Chronic

Inflammation

Dept. of Pathology

College of Medicine

Aliraqia University

Nov. 2. 2015

Objectives

Chronic Inflammation;

• Definition
• Characteristic changes (Morphology).
• Causes.
• Ch. Inflamm. Cells & Mediators.
• Granulomatous Inflammation.
• Systemic effects of inflammation.

Chronic inflammation

;

• long lasting inflammation (weeks to years) due to

persistent stimuli.

• Continuing

inflammation

, tissue

injury

& healing by

fibrosis



MORPHOLOGIC FEATURES

• Mononuclear cells infiltration.
• Tissue destruction and
• repair (

fibroblast proliferation

)

• It can follow acute inflammation or can be chronic right

from the beginning

Causes of Chronic inflammation

• Arises in followings ways.

– Persistent infection

; (TB, T. pallidum, viruses & Fungi)

i.e. chronic right from the beginning

-- Immune mediated inflammatory diseases

-- Prolonged exposure to

toxic agents

; (Silica, lipid)

-- After

acute inflammation

persistent

of injurious agents

or interference with healing (peptic ulcer).

progression

acute inflammation.

Recurrent

attacks of acute

inflammation.

Several coalescent silicotic nodules

Atherosclerotic plaque in the coronary artery



Prolonged exposure

to toxic agents
 Neurodegenerative

disorders (Alzheimer

disease), AS, DM, ca

Chronic inflammation

Cellular Players

• MACROPHAGES (aka, HISTIOCYTES)
• LYMPHOCYTES
• PLASMA CELLS
• EOSINOPHILS
• MAST CELLS

CHRONIC INFLAMMATION

Cells

(Mononuclear)

LYMPHOCYTE

MONOCYTE

MACROPHAGE

HISTIOCYTE

Macrophage origin

Mononuclear phagocyte system

Pathways of macrophage activation

increased cell size,
lysosomal enz,
phagocytose

• Pathways of macrophage activation. Different stimuli activate

monocytes/macrophages to develop into functionally distinct
populations.

• Classically activated macrophages are induced by microbial

products and cytokines, particularly IFN-

γ, and are microbicidal and

involved in potentially

• harmful inflammation. Alternatively activated macrophages are

induced by IL-4 and IL-13, produced by TH2 cells (a helper T cell
subset) and other

• leukocytes, and are important in tissue repair and fibrosis. IFN-γ,

interferon-

γ; IL-4, IL-13, interkeukin-4, -13.

• IFN-γ can also induce macrophages to fuse into

large,multinucleate giant cells

 Macrophages have several critical roles in defense &

the inflammatory response.

• Phagocytosis.
• Macrophages initiate the process of tissue repair.
• Secrete mediators of inflammation (TNF, IL-1,

chemokines, and others) and eicosanoids.

• Display Ags to T lymphocytes and respond to signals

from T cells, thus setting up cell mediated IR.

Lymphocytes

• TH1

cells produce IFN-γ, which activates macrophages.

• TH2

cells secrete IL-4, IL-5, and IL-13, which activate

eosinophils and macrophages.

• TH17

cells secrete IL-17 and other cytokines that

activate PMN & monocytes into the reaction

• Activated T lymphocytes

, in turn, produce cytokines,

which recruit and activate macrophages and thus
promote more antigen presentation and cytokine
secretion.

• The result is

a cycle of cellular reactions that fuel and

sustain chronic inflammation

• In some strong and prolonged inflammatory reactions,

the accumulation of lymphocytes, APC, and plasma
cells, is seen in the synovium in long-standing
rheumatoid arthritis and in autoimmune thyroiditis.

Chronic inflammation in the lung

Acute inflammation in the lung

Histology of chronic inflammation

  Lymphocytes, plasma cells, and
macrophages
  Proliferation of fibroblasts & small
blood vessels, Increased CT
  Tissue destruction

Types of chronic inflammation

•

Nonspecific,

e.g.chronic peptic ulcer

•

Specific

(granulomatous) Inflamm

GRANULOMA

•

Granulomatous reactions are commonly

seen with mycobacteria, fungi, sarcoid,

foreign bodies, and rarely with almost

anything. Acid fast or fungal cultures may

possibly be positive in “fresh” granulomas,

gram positive or gram negative bacteria

are NOT common causes of granulomas.

• Granulomatous inflammation

is a distinctive

pattern of chronic inflammation characterized by

aggregates of activated macrophages with
lymphocytes.

• Granulomas are characteristic of certain specific

pathologic states;

• Recognition of the granulomatous pattern is

important because of the limited number of
conditions that cause it

Chronic Granulomatous Inflammation

• Granulomas,

by aggregates of activated macrophages with

lymphocytes.

• Granulomas are characteristic of certain specific pathologic states;

• Granulomatous inflammation

is a

distinctive pattern of chronic inflammation
characterized by

aggregates of activated

macrophages with lymphocytes.

• Granulomas are characteristic of certain

specific pathologic states;

• Recognition of the granulomatous pattern

is important because of the limited number
of conditions that cause it

Classification of granulomatous

inflammation, according to the etiology

• Infectious granuloma

– Bacterial

• Mycobacterium tuberculosis (Koch bacillus) - Tuberculosis
• Mycobacterium leprae - Leprosy
• Treponema pallidum - Syphilis
• Gram-positive bacillus (Actinomyces israeli) - Actinomycosis
• Gram-negative bacillus (Bartonella henselae) - Cat-scratch disease

– Parasitic

• Schistosomiasis
• Toxoplasma gondii - Toxoplasmosis

– Fungi (Candida albicans) - Candidiasis

• Foreign body granuloma
• Unknown etiology granuloma

– Sarcoidosis
– Crohn's disease

Two factors necessary for granuloma formation

• Presence of indigestible organisms or particles

(Tb, mineral oil, etc)

• Cell mediated immunity (T cells)

TB Granuloma

Fungal granuloma

Foreign body giant cell

GRANULOMAS

GRANULOMATOUS INFLAMMATION

CASEATING (TB)

NON-CASEATING

LYMPHATIC DRAINAGE

• SITE REGIONAL LYMPH NODES

SYSTEMIC MANIFESTATIONS

(NON-SPECIFIC)

• FEVER, CHILLS
• C-Reactive Protein (CRP)
• “Acute Phase” Reactants
• Erythrocyte Sedimentation Rate (ESR) increases
• Leukocytosis
• Pulse, Blood Pressure
• Cytokine Effects, e.g., TNF(α), IL-1

Systemic effects

• Fever

– cytokine-mediated (IL-1, IL-6, TNF)
– acute-phase reactions including

• Anorexia
• Skeletal muscle protein degradation
• Hypotension

• Leukocytosis

– Elevated white blood cell count
– Bacterial infection (neutrophilia)
– Parasitic infection (eosinophilia)
– Viral infection (lymphocytosis

NORMAL SPE

Serum

Protein

Electrophoresis

In ACUTE

Inflammation

Alpha-1

alpha-2

are increased,
i.e.,

“acute phase”

reactants.

Outcome of chronic inflammation

• Resolution

/regeneration/restitution of normal

structure

• Repair

/organization/healing by connective

tissue/fibrosis/scarring

• It can

continue

indefinitely, e.g. rheumatoid arthritis

Acute inflammation

Chronic inflammation

Repair

Resolution

Abscess

Injury

Factors necessary for resolution

• Removal of the offending agent
• Regenerative ability if cells have been

destroyed

• Intact

stromal framework (ECM)

Categorization of cells based on

regenerative ability

• Labile cells-

-cells which continue to

proliferate throughout life (gut, skin, BM)

• Stable cells-

-cells which retain the capacity

to proliferate throughout life but usually do
not unless stimulated (liver, kidney,
pancreas, bone)

• Permanent cells-

-cells which cannot

reproduce themselves after birth (neurons,
cardiac and skeletal muscle)

Granulomatous Inflammation

•

Clusters of T cell-activated macrophages,

which engulf and surround indigestible

foreign bodies (mycobacteria,

capsulatum

, silica, suture material)

•

Resemble squamous cells, therefore

called “epithelioid” granulomas

Lymph Nodes and Lymphatics

•

Lymphatics drain tissues

–

Flow increased in inflammation

–

Antigen to the lymph node

–

Toxins, infectious agents also to the node

•

Lymphadenitis, lymphangitis

•

bacteremia

Usually contained there, otherwise

ensues

•

Tissue-resident macrophages must then prevent

overwhelming infection

Macrophage-lymphocyte interactions in chronic inflammation

Patterns of acute and chronic

inflammation

• Serous

– Watery, protein-poor effusion (e.g., blister)

• Fibrinous

– Fibrin accumulation
– Either entirely removed or becomes fibrotic

• Suppurative

– Presence of pus (pyogenic staph spp.)
– Often walled-off if persistent

Patterns (cont’d)

•

Ulceration

–

Necrotic and eroded epithelial surface

–

Underlying acute and chronic inflammation

–

Trauma, toxins, vascular insufficiency

• Features of Chronic Inflammation

• • Prolonged host response to persistent stimulus
• Caused by microbes that resist elimination, immune

responses against self and environmental antigens, and
some toxic substances (e.g., silica); underlies many
important diseases

• • Characterized by persistent inflammation, tissue injury,

attempted repair by scarring, and immune response

• • Cellular infiltrate consisting of activated macrophages,

lymphocytes, and plasma cells, often with prominent
fibrosis.

• • Mediated by cytokines produced by macrophages and

lymphocytes (notably T lymphocytes), with a tendency to
an amplified and prolonged inflammatory response
owing to bidirectional interactions between these cells