Acute Inflammation

Question 1

4 Possible Causes

Answer 1

• Infection (bacterial, fungal)
• Tissue necrosis (burn, trauma, ischemia)
• Foreign body (reacts to damage caused by foreign body or bacteria on foreign body)
• Immune rxns/hypersensitivity (allergies)

Question 2

5 Local Signs

Answer 2

• Swelling (Tumor)
  
  • Due to inc permeability/leaky vessels
• Redness (Rubor)
  
  • Due to vasodilation/more blood to area
• Heat (Calor)
  
  • Due to vasodilation/ more blood to area
• Pain (Dalor)
  
  • Irritate or damage nerves in area
• • Loss of function
    
    • Irritate or damage nerves in area

Question 3

Systemic Manifestations

Answer 3

Fever, sweats, rigors (shivering), tachycardia, tachypnea, malaise

Question 4

5 Lab Changes

Answer 4

• Inc WBC count (esp neutrophils)
• Inc in production of neutrophils by bone marrow —> Left shift (AKA more of the existing neutrophils are in the less mature form b/c they are just now being produced)
  - Less mature = band
  - More mature = segmented
• Neutrophilic toxic changes - toxic granulation, toxic vacuoles (white) and Dohle bodies (appear as light blue blobs on edge of neutrophils)
• Neutrophils also express more CD64 biomarker; seen on flow cytometry
• Inc acute phase reactants in serum; proteins made b liver during inflammation
  - Fibrinogen, C-reactive protein, ferritin, procalcitonin

Question 5

Blood Vessel Response

Answer 5

• Vasodilation - inc blood flow —> redness and warmth
• Inc permeability so that cells can leave vessel to act on injury; endothelial cells separate so cells and proteins can leak out
  - Prod exudate (protein rich and filled w/ debris); SHOULD BE CULTURED B/C CONTAINS BACTERIAL COMPONENTS TOO
• Leads to margination of WBCs (normally flow in middle of vessel but as vessel dilates they accumulate on periphery); more blood flow but slower rate

Question 6

7 Steps of Neutrophil Action

Answer 6

• 1-margination (accumulate on edges of vessel)
• 2- roll on vessel wall by loosely binding selectins
• 3- adhesion by binding more tightly to integrins
• 4-diapedsis (cross endothelial border)
• 5- swarm to attraction site via chemotaxis (migrate to area of highest concentration of cytokines or other stimuli
• 6- Recognition, engulfment,
  
  • Neutrophils have GPCRs, toll-like receptors, cytokine receptors and phagocytic receptors
• 7- Killing
  
  • Microbes that are opsonized are engulfed into phagosomes which fuse w/ lysosomes —> phagolysosome where they are destroyed via lysosomal enzymes and ROS (“oxidative burst”)

Question 7

4 Morphological Patterns of Inflammation

Answer 7

• 1- Serous inflammation
  
  • Inc permeability leads to outpouring of fluid (clear - few proteins)
  • Blisters or effusion w/in body
• 2- Fibrinous inflammation
  
  • If more pronounced inc in permeability —> large molecules leak (fibrinogen) —> deposits fibrin extracellularly
  • See gray/fuzzy lining membrane; dull as opposed to shiny edges
  • Eosinophilic coating
• 3- Suppurative/purulent inflammation
  
  • Produce PUS (contains dead or dying neutrophils, edema fluid and liquefactive necrosis as well as bacteria itself)
  • Abscess - collection of pus in tissue or organ or confined space; treat w/ surgical drainage and culture it
• 4- Pseudomembranous inflammation
  
  • So much debris that it forms pseudomembrane
  • Often at site of mucosal injury or seen w/ Clostridium associated colitis
  • Gray membrane replaces velvet red surface on histology images; can see dead debris on edges

Question 8

4 Types of Cell-derived Mediators

Answer 8

• Vasoactive amines - vasodilation and inc permeability
  - Histamine - from mast cells and basophils (**can use anti-histamines to dec inflammation)
  - Serotonin - from platelets and neuroendocrine cells
• Arachidonic Acid Metabolites
  - AA released from membranes then acted on by COX enzymes or lipoxygenase —> produce several mediators (prostaglandins, leukotrienes, lipoxins)
• ROS
  - Inflammatory stimuli —> activate neutrophil’s NAPH oxidase —> ROS —> kill microbes
• Cytokines & Chemokines
  - Major cytokines are…tumor necrosis factor, interleukin-1 and interleukin-6 (all stimulate adhesion for WBC rolling and inc permeability)
  - Chemokines recruit other WBCs

Question 9

2 Types of Plasma Mediators

Answer 9

Complement

• In plasma in inactive form then activated by proteolysis; many activate other complement proteins once activated —> amplifying cascade
  
  • Critical step is activation of C3 —> C3a and C3b
    
    • C3a - chemokine and inc permeability and stimulates histamine release
    • C3b- cleaves subsequent complement proteins and coats microbes for phagocytosis (opsonization)
  • Can detect inc complement levels in blood

Coagulation/Kinin Systems

- Inc vascular permeability —> factor XII leaks out and becomes activated —> triggers kinin and coagulation cascade
- Kinins = vasoactive peptides that inc permeability and vasodilation and pain
- Factor XIIa also activates fibrinolytic system —> activated complement system by cleaving C3 (INTER-CONNECTED)

Question 10

3 Possible Outcomes of Acute Inflammation

Answer 10

• 1- Complete Resolution - stimulation of inflammation is eliminated and tissue is repaired/regenerated
• 2- Healing - connective tissue replacement (fibrosis/scars)
• 3- Progression to Chronic Inflammation

Question 11

Treatments (6)

Answer 11

• Treat stimulus of inflammation - remove it or use antibiotics
• Treat symptoms
  
  • NSAIDs - anti-inflammatory and pain relief; but stomach ulcers, bleeding
  • Aspirin - irreversible COX inhibitor; platelets cannot make new COX so lasts 10 days
  • Acetaminophen - also inhibits prostaglandin synthesis
  • Lipoxygenase Inhibitors - inhibit leukotriene production or block leukotriene receptors
  • Corticosteroids - dec formation, release and activity of mediators of inflammation (kinins, histamine, liposomal enzymes, prostaglandins, leukotrienes) BUT immunosuppressive and mask signs of inflammation (BAD COMBO)

Question 12

Neutropenia

Answer 12

• cannot make neutrophils in bone marrow (acquired or congenital)

Question 13

Defective Leukocytes Recruitment (2 Types)

Answer 13

Inherited

- Type 1- deficiency in LFA-1 and Mac-1 integrins
- Type 2- deficiency in ligand for selectins

Question 14

Chronic Granulomatous Disease

Answer 14

• inherited defect in genes encoding components of neutrophil oxidative burst (lack of ROS = ineffective microbe killing); since microbes not killed - macrophages eventually come and form granulomas