lecture 50 chronic inflammation.ppt 4.11.11
DESCRIPTION
TRANSCRIPT
Objectives
This lecture provides an understanding of
Cells involved, etiologies, cellular
constituents, general histologic features, of
chronic inflammation
Granulomatous inflammation
Role of lymphatics in the inflammation
Learning outcomes
At the end of the lecture ,student will be able to
Identify and distinguish the cells involved in chronic inflammation
List various causes of chronic inflammation
Describe the morphological features of chronic inflammation
Define chronic granulomatous inflammation
List examples of diseases with granulomatous inflammation
Describe the morphology of granulomatous inflammation
Describe the role of lymphatics in the inflammation
Tissue response to an injury
Definition of chronic inflammation
an inflammatory response of prolonged duration (weeks – months - years)
provoked by the persistence of the causative stimulus
simultaneous presence of active inflammation, tissue destruction and repair
DEFINITION
Inflammation of prolonged duration
( weeks or months) in which
- active inflammation
- tissue destruction and
- attempts at healing
proceed simultaneously
Chronic Inflammation arrives in 3 ways:
1.May follow acute inflammation
e.g pneumonia -> chronic lung abscess
2. Repeated bouts of acute inflammⁿ
e.g cholecystitis , pyelonephritis
3. Begin insiduously as a low grade smouldering reponse
Chronic inflammation arises in the following settings: (CAUSES)
Persistent infections
Immune-mediated inflammatory
diseases
Prolonged exposure to non-degradable
but potentially toxic substances
Persistent infections by microbes
that are difficult to eradicate
Eg: mycobacteria,
Treponema pallidum (causative organism
of syphilis)
certain viruses, fungi and parasites
Immune-mediated inflammatory diseases
autoimmune diseases
(under certain conditions, immune reactions
develop against the individual's own tissues)
Eg:rheumatoid arthritis, multiple sclerosis
allergic diseaseshypersensitivity reaction that are caused by excessive
and inappropriate activation of the immune system)
Eg:bronchial asthma
Prolonged exposure to toxic substances
(non-degradable)– Exogenous (asbestos, silicon)
– Endogenous (chronically elevated plasma lipid components which
may contribute to atherosclerosis)
Cells of Chronic Inflammation
macrophages
lymphocytes
plasma cells
eosinophils
neutrophils
Maturation of Mononuclear Phagocytes
Macrophage
• Mononuclear Phagocyte System (MPS)
Circulating blood monocytes →Tissue macrophages
↓
Kupffer cells (liver)
Sinus Histiocytes (spleen)
Microglia (CNS)
Alveolar Macrophages (lung)
During chronic inflammation
macrophages serve to eliminate
injurious agents and initiate repair
however, they are as well responsible
for much of the tissue injury that
occurs
Macrophage
IFN-g
Activated T cell or NK cell
Tissue macrophage
Activated macrophage
Non Immune activation:Endotoxins, fibronectin, chemical mediators
Tissue injuryToxic oxygen metabolitesMetallo-proteasesCoagulation factorsAA metabolites and NO
Fibrosis (Scaring)Growth factors involved in fibroblast proliferation(PDGF,TGFb,FGF)Angiogenesis factors(FGF,VEGF)Collagen deposition (IL-13 and TGFb)
Macrophage:component of MPStransformed from monocytes
prime cell of chr: inflammⁿActivated by lymphokines bact: endotoxin Activated macrophages
secrete:EnzymesO2 metabolites , cytokinesgrowth factorsNO , PAF,IFN α resultingt/s destructionneovascularisation fibrosis
In chronic inflammation macrophage accumulation persists by
different mechanisms
Continued recruitment of monocytes
from the circulation
Local proliferation
Prolonged survival and immobilization
Lymphocytes:
Naive lymphocytes encounter antigen-presenting cells
and become antigen-specific lymphocytes
Activated T lymphocytes
Regulate macrophage activation and recruitment by secreting specific mediators cytokines (lymphokines) (IFN-γ)
Modulate anti-body production and cell-mediated cytotoxicity and maintain immunologic memory
Plasma cells:
develop from activated B lymphocytes
produce antibody directed either against persistent antigen in the inflammatory site or against altered tissue components
Mast Cells:
- Widely distributed in connective tissues and
participate in both acute and persistent inflammatory reactions
- Binds the Fc portion of the IgE antibody
Cells of Chronic Inflammation
Eosinophils:
- parasitic infections
- Mediated by IgE
- Eotaxin – a chemokine that has the ability to prime eosinophils for chemotaxis
- have granules that contain major basic protein, a highly cationic protein that is toxic to parasites but also causes lysis of mammalian epithelial cells
Chronic inflammation is characterized by
Infiltration with mononuclear cells(including macrophages, lymphocytes, and plasma cells)
indicates persistent reaction to injury
Tissue destruction(largely induced by the products of the inflammatory cells)
Repair (Healing)(involving new vessel proliferation (angiogenesis) and fibrosis)
Attempt to replace lost tissue
Chronic inflammation in the lungshowing all three characteristic histologic features: (1)collection of chronic inflammatory cells (2)destruction of parenchyma (normal alveoli are replaced by spaces lined by cuboidal epithelium(3) replacement by connective tissue (fibrosis)
Chronic ulcer such as
chronic peptic ulcer of the stomach with
breach of the mucosa, a base lined by
granulation tissue and with fibrous tissue
extending through the muscle layers of the
wall
Chronic abscess cavity for example
osteomyelitis, empyema thoraccis
Thickening of the wall of a hollow viscus by
fibrous tissue in the presence of a chronic
inflammatory cell infiltrate, for example
Crohn's disease, chronic cholecystitis
Fibrosis
The most prominent feature of the chronic
inflammatory reaction when most of the
chronic inflammatory cell infiltrate has
subsided. This is commonly seen in
chronic cholecystitis
'hour-glass contracture' of the stomach, lead to acquired
pyloric stenosis
the strictures that characterise Crohn's diseas
Gallbladder showing chronic cholecystitisThe wall is greatly thickened by fibrous tissue
Chronic inflammation in the wall of a gallbladder that has experienced previous episodes of acute cholecystitis Aggregates of lymphocytes and ingrowing fibroblasts
Chronic peptic ulcer of the stomachContinuing tissue destruction and repair cause replacement of the gastric wall muscle layers by fibrous tissueAs the fibrous tissue contractspermanent distortion of the gastric shape may result
A distinctive pattern of chronic inflammation
characterized by focus of chronic
inflammation consisting of a microscopic
aggregation of macrophages that are
transformed into epithelium-like cells,
surrounded by a collar of mononuclear
leukocytes, principally lymphocytes and
occasionally plasma cells fibroblasts
CHRONIC GRANULOMATOUS INFLAMMATION
CHRONIC GRANULOMATOUS INFLAMMATION
A distinctive pattern of chronic
inflammation characterised by
granulomas which are small nodular
collections in which the predominant
cell is the activated macrophage with
epithelial like (epitheloid) appearance
with abundant pink cytoplasm
Granuloma:
A granuloma is a focus of chronic
inflammation consisting of
a microscopic aggregation of macrophages
that are transformed into epithelium-like
cells (epitheloid cells) surrounded by a
collar of mononuclear leukocytes,
principally lymphocytes and occasionally
plasma cells
MORPHOLOGY
Epitheloid cell:(Activated
Macrophage)
-pale pink granular cytoplasm
-indistinct cell boundary
-oval or elongated nucleus +/- folding of
nuclear membrane
-may fuse to form giant cells
Giant cells:
- 40 to 50 µ in diam
- abundant cytoplasm
Langhans' type - 20 or more nuclei in
periphery ( horse shoe pattern)
Foreign body type - nuclei scattered in
cytoplasm
Caseous necrosis
Grossly - this has a granular, cheesy
appearance
Microscopically - appears as amorphous,
structureless, granular debris, with
complete loss of cellular details
central caseous necrosis
Epitheloid Cells
Typical tuberculous granuloma showing an area of central necrosis surrounded bymultiple Langhans-type giant cells, epithelioid cells, and lymphocytes.
central necrosis
Langhans-type giant cells
lymphocytes
Granuloma with caseous necrosis
The lung of a patient with miliary tuberculosis1 to 2 mm granulomas are scattered around like millet seeds (millet is a type of cereal grain)With poor immune responseextensive spread of infection with the production of a "miliary" pattern of granulomas
Scattered granulomas
Types of granuloma:
1. Foreign body granuloma
2. Immune granuloma
(a) indigestible particles or organisms
(b) T cell mediated Immune Response
3. Toxic granuloma – due to silicon, beryllium
In tuberculosis, granuloma is
referred
to as tubercle,
• Hard tubercle
• Soft tubercle – characterized by presence
of central caseous necrosis; caseation
necrosis is rare in other granulomatous
disease
Examples of Diseases with Granulomatous Inflammation
Tuberculosis
Leprosy
Syphillis
Cat – scrath disease
Sarcoidosis
Crohn disease (inflammatory bowel
disease)
Examples of Chronic Granulomatous Inflammation:
Bacterial
TB, leprosy, syphilis,
Parasitic
Schistosomiasis
FungalCryptococcosis,Histoplasmosis,Blastomycosis,
Unknown
Sarcoidosis
Common Causes of Epithelioid Cell Granulomas.Disease Causes
Immunologic response
Tuberculosis Mycobacterium tuberculosis
Leprosy (tuberculoid type) Mycobacterium leprae
Histoplasmosis Histoplasma capsulatum
Coccidioidomycosis Coccidioides immitis
Q fever Coxiella burnetii (rickettsial
organism)
Brucellosis Brucella species
Syphilis Treponema pallidum
Sarcoidosis2
Unknown
Crohn's disease2
Unknown
Berylliosis3
Beryllium (? +protein)
Nonimmunologic response
Foreign body (eg, in intravenous
drug abuse)
Talc, fibers (? +protein)
COMPARISON OF ACUTE AND CHRONIC INFLAMMATION
FEATURE ACUTE
INFLAMMATION
CHRONIC
INFLAMMATION
Onset &duration Immediate &
Transient (few
days)
Delayed &
weeks,months, years
Pathogenesis Microbial pathogens,
trauma, burns
Persistent acute inflammation,
foreign bodies (e.g., silicone,
glass), autoimmune disease,
certain types of infection (e.g.,
tuberculosis, leprosy)
FEATURE ACUTE INFLAMMATION CHRONICINFLAMMATION
Primary cells NeutrophilsMonocytes/macrophages cells), B and T lymphocytes plasma cells, fibroblasts
Necrosis Present Less prominent
Scar tissue Absent Present
Outcome Complete resolution, Scar tissue formation
disability, amyloidosis
progression to
chronic inflammation
abscess formation
COMPARISON OF ACUTE AND CHRONIC INFLAMMATION
Differences between Acute and Chronic Inflammation
Acute Chronic
Duration Short (days) Long (weeks to months)
Onset Acute Insidious
Specificity Nonspecific Specific (where immune response is activated)
Inflammatory cells Neutrophils, macrophages Lymphocytes, plasma cells, macrophages,
fibroblasts
Vascular changes Active vasodilation, increased permeability New vessel formation (granulation tissue)
Fluid exudation and edema + –
Cardinal clinical signs
(redness, heat, swelling,
pain)
+ –
Tissue necrosis – (Usually)
+ (Suppurative and necrotizing inflammation)
+ (ongoing)
Fibrosis (collagen
deposition)
– +
Operative host responses Plasma factors: complement, immunoglobulins, properdin,
etc; neutrophils, nonimmune phagocytosis
Immune response, phagocytosis, repair
Systemic manifestations Fever, often high Low–grade fever, weight loss, anemia
Changes in peripheral blood Neutrophil leukocytosis; lymphocytosis (in viral infections) Frequently none; variable leukocyte changes,
increased plasma immunoglobulin
In acute inflammation the lymphatic channels
become dilated & drain away the oedema fluid of
the inflammatory exudate
This drainage tends to
limit the extent of oedema in the tissues
carry large molecules and some particulate matter
&
antigens are carried to the regional lymph nodes
for recognition by lymphocytes