Inflammation 3

Question 1

POSSIBLE SEQUELAE OF ACUTE INFLAMMATION

Answer 1

Resolution
Repair (fibrosis- scar tissue)
Abscess formation- granuloma walls off lesion
Progression to chronic inflammation- if injurious agent is not removed.

Question 2

EVENTS IN THE RESOLUTION OF INFLAMMATION

Answer 2

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.

Question 3

CAUSES OF INFLAMMATION

Answer 3

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)

Question 4

INFLAMMATORY MEDIATORS

Answer 4

Orchestrate the inflammatory response.
Widely distributed throughout body in inactive form.
Released/synthesised/activated locally at site of inflammation.
Rapidly inactivated to minimise inflammation.

Question 5

WHERE ARE THE 2 PLACES INFLAMMATORY MEDIATORS ARE DERIVED FROM?

Answer 5

1. CELL DERIVED- any cell involved in inflammation can produce inflammatory mediators. eg. tissue macrophages, endothelial cells, recruited leukocytes.
2. PLASMA PROTEIN DERIVED- LIVER. Circulating proteins if three interrelating systems:
   Complement system
   Coagulation/fibrinolysis system
   Kinin system

Question 6

CELL DERIVED INFLAMMATORY MEDIATORS

Answer 6

Can be preformed in secretory granules or newly synthesised.

• PREFORMED- histamine, serotonin.
• NEWLY SYNTHESISED- prostaglandins, leukotrienes, platelet activating factor, ROS, NOx, cytokines, neuropeptides.

Question 7

PLASMA PROTEIN DERIVED INFLAMMATORY MEDIATORS

Answer 7

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.

Question 8

PLASMA PROTEIN DERIVED INFLAMMATORY MEDIATORS contd.

Answer 8

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.

Question 9

KININ CASCADE

Answer 9

Initiated by active Factor XII.
Produces bradykinin.
Bradykinin then stimulates the fibrinolytic system.

Question 10

CLOTTING CASCADE

Answer 10

Initiated by active Factor XII.
prothrombin -> thrombin.
Thrombin stimulates FIBRIN production from fibrinogen/plasmin.

Question 11

FIBRINOLYTIC SYSTEM

Answer 11

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.

Question 12

NEGATIVE EFFECTS OF PHAGOCYTOSIS

Answer 12

-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.

Question 13

SPECIAL INFLAMMATORY LESIONS

Answer 13

• 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)

Question 14

ABSCESS

Answer 14

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.

Question 15

BACTERAEMIA

Answer 15

The presence of bacteria in the blood.

Question 16

TOXAEMIA

Answer 16

The presence of toxins in the blood.

Question 17

VIRAEMIA

Answer 17

The presence of viruses in the blood.

Question 18

SEPTICAEMIA

Answer 18

Bacteraemia or viraemia complicated by toxaemia, fever, severe illness, often shock.

Question 19

MACROPHAGES

Answer 19

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.

Question 20

GRANULOMAS

Answer 20

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.

Question 21

SPECIFIC GRANULOMATOUS DISORDERS

Answer 21

• Mycobacteria tuberculosis- CASEATING tuberculosis lesions.
• Actinobacilla- Wooden tongue.
• Actinomycosis- Lumpy jaw.
• Caseous lymphadenitis
• Feline infectious peritonitis.

Question 22

NON CASEATING GRANULOMA

Answer 22

Central epithelioid cells and multinucleate giant cells with peripheral T cells.
Intracellular bacteria can be seen within the epithelioid cells.

Question 23

CASEATING GRANULOMA

Answer 23

Granuloma with central thick, dehydrated, ‘cheese like’ necrotic debris in centre.
Activated macrophages and multinucleate giant cells (Langhan’s cells) centrally.
Peripheral lymphocytes.

Question 24

WOODEN TONGUE

Answer 24

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.

Question 25

LUMPY JAW

Answer 25

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)

Question 26

FELINE INFECTIOUS PERITONITIS (FIP)

Answer 26

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.

Question 27

WET FIP

Answer 27

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.

Question 28

DRY FIP

Answer 28

Partial cell mediated immunity develops- intermediate between non-protective humoral and protective CMI.

Question 29

LESIONS IN FIP

Answer 29

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.