Inflammation 3 Flashcards
Regulation of the inflammatory response. Causes of inflammation Regulation of inflammation- Mediators- cell derived and plasma protein derived. Acute vs chronic inflammation.
POSSIBLE SEQUELAE OF ACUTE INFLAMMATION
Resolution
Repair (fibrosis- scar tissue)
Abscess formation- granuloma walls off lesion
Progression to chronic inflammation- if injurious agent is not removed.
EVENTS IN THE RESOLUTION OF INFLAMMATION
Phagocytosis and clearance of necrotic cell debris and microbes by neutrophils and macrophages.
Angiogenesis and fibrosis (fibroblasts) -> repair.
Fluid and proteins causing oedema drain via lymphatic system, or are taken up by macrophages via pinocytosis.
CAUSES OF INFLAMMATION
Not just infection!
MICROBIAL INFECTIONS
HYPERSENSITIVITY (Type I- IV)
PHYSICAL AGENTS- burns etc.
CHEMICALS- acids, alkalis, oxidising agents
TISSUE NECROSIS- ischaemia (kidneys/gut especially prone)
INFLAMMATORY MEDIATORS
Orchestrate the inflammatory response.
Widely distributed throughout body in inactive form.
Released/synthesised/activated locally at site of inflammation.
Rapidly inactivated to minimise inflammation.
WHERE ARE THE 2 PLACES INFLAMMATORY MEDIATORS ARE DERIVED FROM?
- CELL DERIVED- any cell involved in inflammation can produce inflammatory mediators. eg. tissue macrophages, endothelial cells, recruited leukocytes.
- PLASMA PROTEIN DERIVED- LIVER. Circulating proteins if three interrelating systems:
Complement system
Coagulation/fibrinolysis system
Kinin system
CELL DERIVED INFLAMMATORY MEDIATORS
Can be preformed in secretory granules or newly synthesised.
- PREFORMED- histamine, serotonin.
- NEWLY SYNTHESISED- prostaglandins, leukotrienes, platelet activating factor, ROS, NOx, cytokines, neuropeptides.
PLASMA PROTEIN DERIVED INFLAMMATORY MEDIATORS
Can come from complement activation or Factor XII (Hageman factor) activation.
- COMPLEMENT ACTIVATION- C3a/C5a- anaphylotoxins, C3b, C5b-9 (Membrane Attack Complex)
- FACTOR XII ACTIVATION- kinin system and coagulation/fibrinolysis system.
PLASMA PROTEIN DERIVED INFLAMMATORY MEDIATORS contd.
COMPLEMENT PROTEINS- activated by antibody or by microbes.
Cause leukocyte chemotaxis, opsonisation and phagocytosis of microbes, cell killing.
COAGULATION PROTEINS- activated by activated Factor XII.
Cause clotting/kinin/complement cascade activation.
Activates fibrinolytic system.
KININS- from proteolytic cleavage of precursors.
Mediate vascular reaction and pain.
LIVER FUNCTION WILL AFFECT THESE MEDIATORS.
KININ CASCADE
Initiated by active Factor XII.
Produces bradykinin.
Bradykinin then stimulates the fibrinolytic system.
CLOTTING CASCADE
Initiated by active Factor XII.
prothrombin -> thrombin.
Thrombin stimulates FIBRIN production from fibrinogen/plasmin.
FIBRINOLYTIC SYSTEM
Activated by bradykinin, from the kinin cascade.
causes PLASMIN production from plasminogen.
This can then form fibrin.
It also activates the COMPLEMENT CASCADE, C3 -> C3a.
NEGATIVE EFFECTS OF PHAGOCYTOSIS
-Regurgitation during feeding if phagolysosome briefly stays open.
-Frustrated phagocytosis- substances are difficult to ‘chew’ on difficult surfaces.
Highly activated- many substances released.
-Phagolysosome membrane damage e. by sharp substances- urate crystals in gout.
All of the above cause release of lysosomal granules and enzymes.
-> LEUKOCYTE INDUCED TISSUE INJURY.
Highly activated phagolysosomes release more substances.
eg. Asthma, glomerulonephritis, septic shock, arthritis, pulmonary fibrosis.
SPECIAL INFLAMMATORY LESIONS
- ABSCESS- walled off acute inflammation in solid organs.
- CELLULITIS- pus extends through fascial planes. “dissects along fascial planes”
- EPITHELIAL SURFACES- diphtheritic membranes.
ulceration. (eg. gastric ulceration)
ABSCESS
Develops when the acute inflammatory response fails to eliminate the cause of inflammation.
Enzymes and inflammatory mediators liquefy the affected tissue and neutrophils.
“Abscessation is a defense to prevent the uncontrolled multiplication of bacteria. If the bacteria were to proliferate unchecked, septicaemia would result.”
Neutrophils infiltrate from blood, engulf bacteria and release enzymes which can destroy bacteria and tissues. First line of defense.
Abscess formation- necrotic centre of debris, degenerative neutrophils and bacteria.
Scavenging macrophages present at edge.
Plasma cells and lymphocytes produce antibody.
The entire thing is contained within a fibrous capsule, possible with a pyogenic membrane over this.
Resolution- to fibrous scar tissue.
BACTERAEMIA
The presence of bacteria in the blood.
TOXAEMIA
The presence of toxins in the blood.
VIRAEMIA
The presence of viruses in the blood.
SEPTICAEMIA
Bacteraemia or viraemia complicated by toxaemia, fever, severe illness, often shock.
MACROPHAGES
Free and fixed.
Fixed, resident cell populations, sometimes known as histiocytes.
These cells process and present antigens to the immune system.
They are a major source of cytokines.
Part of the INNATE immune system.
Presence of macrophages indicates granulomatous infection.
GRANULOMAS
Organised granulomatous inflammation.
A central core of necrotic debris and neutrophils.
Macrophages make up most of the lesion (this includes multinucleate giant cells)
The periphery of the granuloma contains lymphocytes, plasma cells and fibroblasts.
SPECIFIC GRANULOMATOUS DISORDERS
- Mycobacteria tuberculosis- CASEATING tuberculosis lesions.
- Actinobacilla- Wooden tongue.
- Actinomycosis- Lumpy jaw.
- Caseous lymphadenitis
- Feline infectious peritonitis.
NON CASEATING GRANULOMA
Central epithelioid cells and multinucleate giant cells with peripheral T cells.
Intracellular bacteria can be seen within the epithelioid cells.
CASEATING GRANULOMA
Granuloma with central thick, dehydrated, ‘cheese like’ necrotic debris in centre.
Activated macrophages and multinucleate giant cells (Langhan’s cells) centrally.
Peripheral lymphocytes.
WOODEN TONGUE
Actinobacillus lignieresii. Gram negative bacilli.
Oral tissue, especially tongue musculature affected.
“Severe chronic pyogranulomatous and fibrosing myositis”.
Caused by oral wounds, penetrating plant fragments -> infection.
Causes difficulty prehending/swallowing, excessive salivation.
Eosinophilic club colonies seen centrally.
LUMPY JAW
Actinomycosis- Gram positive bacilli.
Invasion of mandible/maxilla/other bones, due to trauma during feeding/tooth injury/other injury.
Painless swelling over several weeks, becomes painful, with fistulous tracts, exudate discharge (sulphur granules)
Involvement of draining lymph nodes is rare.
If localised, surgery can be effective.
PYOGRANULOMATOUS/GRANULOMATOUS OSTEOMYELITIS.
Splendore-Hoeppli bodies can be seen (antigen-antibody complexes- club colonies- surrounding foreign material, in this case bacteria)
FELINE INFECTIOUS PERITONITIS (FIP)
Caused by Feline Coronavirus (FeCoV)
Worldwide distribution, 2 are recognised:
FECV- Feline Enteric Coronavirus. AVIRULENT.
FIPV- Feline Infectious Peritonitis Virus. VIRULENT.
Transmission via infected saliva/faeces, or directly in utero.
Replicates in macrophages.
Viral spread to liver, visceral peritoneum, pleura, uvea (vascular tunic of eye), meninges.
Type and degree of immunity determines disease pattern.
Strong cell mediated immunity = viral containment with resistance.
Humoral immunity = insufficient alone, may enhance disease.
Disease mostly seen in cats between 3 months and 3 years of age, but sporadically occurs in all ages. Can result in death.
WET FIP
Ascites seen. Yellow, fibrinous exudate.
Virus-antibody-complement complexes accumulate with infected macrophages.
They may or may not be ingested by macrophages.
Significant viral replication.
Blood vessel damage- fluid leaks out.
DRY FIP
Partial cell mediated immunity develops- intermediate between non-protective humoral and protective CMI.
LESIONS IN FIP
Pyogranulomatous inflammation.
Vasculitis.
Inconsistent vascular necrosis.
WET- Serositis- fluid accumulation in thoracic and abdominal cavities.
DRY- Pyogranulomas around vessels affecting a wide range of organs.
