topic 4.2: chronic inflammation Flashcards
what occurs during chronic inflmmation (overview of chronic inflammation)
invloves active inflammation, tissue injury and healing proces simulatenously
tissue destruction induced by products of inflammatory cells (eg proteases)
tissue repair/healing process: fomration of fibrorus tissue, new vessel proliferation
overview of chronic inflmmation
-slow preogression
-persistant inflammation response for longer than 10-14 days (acute inflmmation), up to a year or more
-non exudative
-active inflammation, tissue injury and healing procress simulatenously
tissue destruction: induced by products of inflmmatory cells
tissue repair: formation of fibrous tissues, new vessle proliferation
major cells invloved: macrophage, lymphocytes , plasma cells
what causes chronic inflmmation
unresolved accute inflmmation (acute inflammation progressing to chronic inflmation)
-persistent infections (microbes that are difficult to eradicate) (body stuck in a cycle of destruction and repair)
-harmful stimulus that tirggers a chronic inflmmatory response from the onset (eg viral infections, autoimmune disease) (eg straight away go into chronic inflmmation)
prolonged exposure to toxic agents eg. atherosclerosis – chronically elevated plasma lipids (toxic agent) (too long, body have to keep fighting)
PPUH: persistant infection, prolonged exposure to toxic agent, unresolved acute inflammation, harmful stimulus that triggers chronic inflammatory response from its onset
what are the two examples of hypersentivity rxns/types we learn about
glomerulonephritis and vasculitis
tell me about the mechanism of glomerulonephritis
what is glomerulonephritis: inflammation of the glomeruli in the kidney
cause: consequence of some other disease, such as infection/cancer. many dogs with glomerulonephritis, the trigger cannot be determined
mechanism: immune complexes (antinody-antigen complex) become trapped in the glomeruli-> activation of the body’s inflmmatory defence system-> damages the glomeruli
immune complex deposition in gomeruli-> basement membrane thicend and stimulates glomerlar cells to proliferate (form new cells) -> form lesions-> this it is called Membranoproliferative glumerulonephritis
any or all of the three glomerular cells populations-epithelail,enodthelial and mesangial cells can proliferate
MPGN lesion are classified into three types (I, II & III) based on histopathology &
pathogenesis.
impact of glomerulonephritis: protein in the urine during a urine test is the first indication
treatment: 1.treating any underlying disease
2.reducing the amount of protein lost in the urine
3.managing existing kidney disease
4.giving and immunosuppressive drugs to reduce the formation of immune complexes
untreated-> chronic kidney failure
what is glomerulonephritis
inflmammation of the glomeruli in the kidneys
explain the mechanism of glomerulonephritis
-the inflammation develops when immune complexes (antibody and antigen) become trapped in the gloeruli (too big, cannot come out) (actually not harmful but immune system mistake it to be harmful-> hypersitivity)
- this leads to activation of the bodys inflmmatiory defense system (to clear the complexes) which in turns damages the glomeruli
- also the immune complex deposition in the glomeruli cause basement membrane thickening and stimulate gommerular crlls to proliferate
- any or all three of the glmerular cell population- epithelial, enodthelial and mesangial cells can proliferate
- the formation of lesions therefore called Membranoproliferative glumerulonephritis (MPGN).
- MPGN lesions are classifyed into three types (I, II,III) based on histophathology (tissue) and pathogenesis (process)
causes of immune complex formation on glomerulonephritis
formed as a consequence of some other disease (eg infection, cancer)
however, many dogs with glomerulonephritis, the triggers cannot be determiend
result of glomerulonephritis
results in excessive loss of protein in urine (proteinuria)
testing for glomerulonephritis
protein in the urine during a urine test may be the first indication that dogs has glomerulonephritis
treatment of glomerulonephritis
-treating any underlying diseases
-reducing amt of ptotein lost in urine
-managing existing kidney disease
-giving immunosupressive drugs to reduce the formation of the immune complees
effect of not treating glumerulomephritis
can lead to chronic kidney failure
tell me about vasculitis
what is vasculitis: inflmmation of the blood vessles casued by immune complexes (rem immune complex cause other cells to come to clear it-> inflmmation-> hence inflmmation of the blood vessels)
causes: drugs are a frequent cause of vasculitis in dogs
signs: skin abnormalities are seen as purplish red dots, (bleeding under the skin) ulcerations (sores/wonds) and scabs (crust-due to healing)
where: depending on which blood vessles invloved, signs appear on the lower leg, paws, ears, mouth or tongue
diagnosis: The disorder is diagnosed by performing tests on samples removed from the affected areas (biopsies)
treatment: Vasculitis is treated by stopping the offending drug (if implicated as the cause) or by giving drugs that suppress the immune system (reduce the formation of complexes causing the imflammtion)
what is vasculitis
inflammation of the blood vessels caused by immune complexes occuring in dogs
what are the clinical signs of vasculitis
skin abnormalities are seen as purplish red dots, ulcerations and scabs .
depending on which blood vessels are invloved, signs appear on lower legs, paws, ears, mouth or tongue
cause of vasculitis
drugs are a frequent cause of vasculits
what are the test done to confirm vasculitis
performing tests on samples removed from the affected area (biopsies)
treatment of vasculitis
stopping the offending drug (if it is the cause)
or giving drugs to supress the immune system
what cells are invloved in chronic inflammation
macrphage
lymphocytes
eosinophils
charactersitics and function of machropage in chronic inflmmation
Dominant cells of chronic inflammation.
- Blood monocytes (og form of cell when in blood)→ (migrate to tissues) →macrophage
- Phagocytes
- When activated: increased cell size,
lysosomal enzyme content & phagocytic
capacity. (better able to recognise and engulf pathogens) - H&E stain: large, flat, pink
- function: Activated macrophages secrete products
that cause tissue injury & inflammation
(eg. proteases, cytokines) and fibrosis (eg.
growth factors) - Can be stimulated by lymphocytes to fuse
into large, multinucleated giant cells
(MNGC) (response in chronic inflamation) (bigger cells, more powerful phagocytic capabilities)
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function and characteristics of lymphocyte in chronic inflmmation
Macrophages and lymphocytes interact in a
bidirectional way that sustain chronic
inflammation. (keep activating each other)
➢ Macrophage stimulate T cell response
by displaying antigens.
➢ Activated T cells produce cytokines that
activate macrophages
Plasma cells (from activated B cells)
produce antibodies directed against
persistent antigens.
crucial to sustain chronic inflammation, eg chronic inflammation
function and characteristic of eosinophils in chronic inflmation
Usually found in parasitic or allergic
inflammatory sites
what are the two main types of chronic inflmmation
non-granulomatous and granulomatous
how does non granulomatous chronic inflmation look like under the microscope
Microscopically: Loose clusters of inflammatory cells with no particular arrangement.
* Macroscopically: Variable (could be either) background of fibrosis, or reactive hyperplasia or hypertrophy in surrounding tissues.
*
* Eg: Chronic inflammation of skin – skin thickens, become greasy because of hyperplasia of skin
glands; chronic inflammation of gut – wall is thicker than normal.
what does granulomatous chronic inflamation look like under the microscope (microscopincally)
Distinct arrangements of inflammatory cells – ‘granulomas’
* (Microscopically) Granulomas = central aggregates (clumping) of macrophages with mononuclear (lymphocyte, plasma cells) inflammatory cells clustered around the macrophages, and a rim of fibrous tissue around the outside. (macrophage, mononuclear cells and then fiborous tissue)
May be present (microscopically):
* Multinucleated giant cells = fusion of macrophages (due to lymphocytes)
* Neutrophils + macrophages in the centre of granulomas → known as pyogranulomatous (seen in feline infectious peritonitis, FIP).
what does granulmatous chronic inflmation look lole macrscopically
Single, large, visible lumps (the granulomas)
* Numerous, smaller lumps (tissue feels thickened and nodular)
* Formed when: cause of inflammation resists destruction (eg suture cannot be broken down) by inflammatory or immune mediated processes (attaching its own cell)
- Eg. foreign material (suture, splinter); infectious organisms (bacteria with protective capsules eg
tuberculosis, parasites with tough outer walls); hypersensitivity response.
what are harmful effects of chronic inflmmation
1.Long term disease and lasting dysfunction of affected organ/tissue.
* Chronic nephritis → persistent renal disease
* Chronic enteritis → diarrhea, weight loss, inability to absorb nutrients efficiently.
2.Loss of organ/tissue function due to pain, swelling, fibrosis (scarring), discharge
3.Weight loss, persistent fever due to chronic effects of chemical mediators (porstaglandins)
- Changes in blood – increased leukocytes, globulins (producing antibodies), decreased RBCs (anaemia) (more energy for leuk poduction than RBC)
