Lecture 12 - chronic inflammation and healing Flashcards
When does a chronic inflammation occur
Occurs when acute inflammation fails to resolve an insult: – Foreign bodies – Autoimmune disease – Persistent infection – Hypersensitivity/Allergic disease
What are the 4 causes of chronic inflammation
– Foreign bodies – Autoimmune disease – Persistent infection – Hypersensitivity/Allergic disease
What does peracute mean the time frame
(immediate) insult – minimal inflammation
What does acute mean in time frame
(<2 days) – acute inflammation
What does subacute mean in time frame
(2-7 days) – transitional period
What does Chronic mean in time frame
(7 days +) – chronic inflammation
What is the sequence of the name for each time frame
- Peracute (immediate) – minimal inflammation
- Acute (<2 days) – acute inflammation
- Subacute (2-7 days) – transitional period
- Chronic (7 days +) – chronic inflammation
What are the 3 features of chronic inflammation
- Changes in inflammatory cell population
- Inflammatory tissue damage
- Tissue healing
– Regeneration, fibrosis and scar tissue formation
why does the celll type change in chronic inflammation
Represents induction of the ADAPTIVE immune response
What changes in cell type
T lymphocytes • Key cells of adaptive immune system • Activated in response to specific binding of antigen with T-cell receptor • Proliferation of lymphocytes • Produce cytokines to direct the immune response • No antigen recognition = minimal chronic inflammation
What are the subtype of chronic inflammation
Lymphocytic/Lymphoplasmacytic Granulomatous Eosinophilic Often mixed, and may have neutrophil component – “Chronic-active” inflammation
What is another word for Lymphocytic inflammation
non-suppurative inflammation
What cells are responsible in lymphocytic inflammation
- cytotoxic T cells
- helper T cells (Th cells)
- B cells
What is it called when plasma cells are present in a lymphocytic inflammation
Lymphoplasmacytic inflammation
What does perivascular mean
situated or occurring around a blood vessel.
What is common during lymphocytic inflammation
Perivascular distribution common
Sometimes form nodular aggregates
– Lymphoid follicles
What does lymphocytic inflammation commonly respond to?
cell-association antigen
What disease are usually prone to lymphocytic inflammation?
• Auto-immune disease – Type 1 diabetes • Viral infections – Rabies – Viral hepatitis in humans • Hypersensitivity diseases – Inflammatory bowel disease • Idiopathic??? – Lymphoplasmacytic stomatitis
What are the roles of macrophages
– Phagocytosis
– Direct inflammation and repair
What does phagocytosis do
• Digest and eliminate foreign agents
• Present antigen to T-cells (function as
antigen-presenting cell)
How does macrophage direct inflammation and repair
• Secrete cytokines such as interleukin 12
(IL-12) to promote inflammation
• Secrete cytokines such as TGF-β to
suppress inflammation and promote repair
What does macrophages respond to?
– Chronic infections (parasites, fungi,
mycobacteria)
– Foreign material
What is Macrophage-dominated inflammation called
GRANULOMATOUS INFLAMMATION
Sometimes also called histiocytic inflammation
What is clusters of macrophages called
GRANULOMAS
• Cells may fuse to form GIANT CELLS
What are the subtypes of granulomatous inflammation
– Pyogranuloma – central accumulation of neutrophils
– Caseating granuloma/necrogranuloma
What is Pyogranuloma
– central accumulation of neutrophils
▪ Seen with some foreign bodies, particularly with bacterial contamination
▪ Also with some infections (eg. Rhodococcus equi)
What is Caseating granuloma/necrogranuloma
▪ “Cheesy” centre composed of dead tissue
▪ Seen particularly with tuberculosis and some parasites
What do Granulomatous inflammation often form
discrete or coalescing
nodules in tissues
- Easy to mistake for NEOPLASIA
Do nodules develop in granulomatous disease?
no
What is eosinophilic inflammation
Primarily parasitic or allergic disease
What does eosinophilic inflammation affected tissues often look like
green appearance
eosinophils are actually green!
What do tissue damage result from?
– Damage by the original insult
– Release of inflammatory mediators
– Cellular phagocytosis or apoptosis
– Tissue death due to circulatory compromise (thrombosis)
Do the body usually attempt to heal even in chronic inflammation?
Yesregardless of whether insult resolved
– Usually ineffective without resolution of insult
What is the 2 major pathways of healing
– Regeneration
– Repair
What is an exmaple of tissue that have specialized healing mechanisms
bone
What is regeneration
Replacement of damaged tissue with the original
cell type
What is regeneration depend on
- Viability of original cells
- Type of tissue
- Preservation of connective tissue scaffold
What are the regeneration cell types
Labile cells
Stable cells
Permanent cells
What is the function of labile cell
Undergo constant turnover and can regenerate
completely from germinal cells
– Epidermis of skin, intestinal epithelium, bone marrow
Where do labile usually be at
Epidermis of skin, intestinal epithelium, bone marrow
What is the function of stable cell
Normally quiescent (ie. not dividing), but have the
ability to regenerate if required
– Hepatocytes, osteocytes, renal tubular epithelium
Where do stable cell usually located at
Hepatocytes, osteocytes, renal tubular epithelium
What is the function of permanent cells
– Considered terminally differentiated – Do not regenerate – Neurons, cardiac muscle
Where is permanent cell located at
Neurons, cardiac
muscle
Do permanent cell regenerate
no
How is tissue repaired
• Replacement of damaged tissue by fibrous connective tissue (scar tissue) – Also referred to as fibrosis • Restores structure at expense of function • Occurs in competition with regeneration
How does repair occur?
• Defect is initially filled by formation of granulation tissue
– Fragile, vascular connective tissue
– COMPLETELY DIFFERENT FROM GRANULOMA
What is the inflammatory phase of repairing tissue
• Clearance of damaged tissue debris
– Neutrophils and macrophages
• Replaced by fibrin coagulum
what is the proligerative phase of repairing tissue
– Production of granulation tissue
– Angiogenesis
• Fibroplasia
What is Angiogenesis for in proliferative phase
• Provides oxygen and nutrients for healing
• Hypoxia in damaged tissue stimulates release of
growth factors (eg. VEGF, FGFs, Angiopoietins) to
promote blood vessel development
What is angiogenesis
Angiogenesis is the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells, which line the inside wall of blood vessels.
What is frbroplasia
– Production of collagen stroma
– Migration of fibroblasts and deposition of immature
type 3 collagen
– Occurs under influence of growth factors (PDGF,
FGFs, TGF-β)
What is fibroplasia growth influenced by?
occurs under influence of growth factors (PDGF,
FGFs, TGF-β)
What is the Maturation phase and scar
formation of repairing tissue
• Reorganization of collagen and change in collagen type (Type 1) – Type 1 collagen stronger – Organized parallel with lines of tension • Contraction of connective tissue • Maturation and regression of vasculature
What is the intention of primary healing
restoring to intact skin after fibrin is grown on the surface
What is the intention of secondary healing
for bigger wound
What is the steps of primary intention heal
- Wound edges joined by fibrin plug
(24hrs) - regrowth of basel layer of epidermis (days)
- Lysis of fibrin and re-epithelialisation (1week)
- Restoration of intact skin (weeks)
What is the difference between primary and secondary intention healing
- More inflammation
- More granulation tissue
- More fibrosis/scarring
- PROLONGED HEALING
What is the steps in secondary intention healing
- Large defect filled by fibrin clot (2-3 days)
- New blood vessels and fibroblast (granulation tissue) grow from the demis into fibrin
- Collagen laid down by granulation tissue fibroblasts to restore integrity (2-4 weeks)
- Maturation of collagen achieves structural integrity and allows regrowth of epidermis
What factors influence healing?
- Infection
- Foreign material
- Nutrition
- Movement/pressure
- Vascular/Oxygen supply
- Hormones
- Concurrent disease
- Age
What are some abnormal healing?
- Proud flesh
* Keloid
What is keloid
– Formation of excessive scar tissue during healing
– Rare in animals, people of African descent predisposed
What is proud flesh
– Formation of excessive granulation tissue that delays healing
– Common in horses
What animal commonly have proud flesh
horse
What are the consequences of scar tissue
- Strictures
- Adhesions
- Restricted movement
What is strictures
– Scar contracture causing narrowing of hollow organ
What is adhesions of scars
– Formation of fibrous tissue attachments between adjacent organs
Why does scar restrict movement
– Contraction of scar tissue around joints and tendons can prevent normal
movement
What directs inflammation?
T lymphocyte
What can T cell differentiate into after getting signalled by a antigen presenting cell
- Th1 cell, Further differentiate into macrophage recuitment and igG antibody production
- Th2 cell, further differentiate into eosinophil recruitment and igE antibody production
- Cytotoxic T cell
What disease are usually prone to lymphocytic inflammation?
auto-immune disease
-type 1 diabetes
Do granulomatous alway lead to granulomatous inflammation
no, example of it is johne’ disease granulomatous enteritis
What is one difference between regeneration and repair?
Repair doesnt restore the function, but just the structure
What is angiogenesis stimulated by?
hypoxia
