Inflammation

Question 1

Inflammation is an end product of the activation of the immune system. It is a physiological response to what 3 things? Give some examples of when it is a pathologic response.

Answer 1

• Infection, wound healing, malignancy

- autoimmunity, autoinflammation, hypersensitivity, ineffectual inflammation

Question 2

What are the 4 cardinal signs of inflammation and what is sometimes included as the 5th sign?

Answer 2

• swelling (tumor)
• Redness (rubor)
• Heat (calor)
• Pain (dolor)
• Loss of function (functio laesa)

Question 3

Briefly explain the pathophysiology of the signs of inflammation

Answer 3

• inflammation leads to the expansion and “leakiness” of blood vessels that allow the humoral and cellular components of the immune system to reach the tissues
• important for this to be localized to avoid shock and death

Question 4

List 3 mediators of inflammation

Answer 4

1. Kallikrein-Bradykinin system
2. Histamine
3. Complement

Question 5

What happens in the Kallikrein-bradykinin system?

Answer 5

• at site of inflammation, kallikrein causes cleavage of kininogen into bradykinin
• bradykinin receptors on endothelium get activated and allow for plasma and cellular exudation
• this occurs in both the tissue and blood vessels since their is plasmaKK and tissue KK which allows for a reinforcement of the vasodilation in a local manner!

Question 6

Role of histamine in inflammation

Answer 6

• one of many factors released upon tissue injury

- H1 histamine R on endothelium become activated and dilate and increase permeability

Question 7

Role of complement in inflammation

Answer 7

• C5a receptor and C3a receptors on various cell types lead to increase in blood vessel permeability when activated
• local activation of the complement cascade will therefore lead to dilation of local vessels and inflammation

Question 8

2 ways to categorize inflammatory response

Answer 8

1. Quantitative: systemic vs. local

2. Qualitative: cytokines and type of cells

Question 9

Systemic vs. local inflammation examples

Answer 9

• Systemic: bacteremia, metastatic cancer, systemic autoimmune disease
• Local: local infection, primary tumor, organ specific autoimmune disease

Question 10

Qualitative categorization of inflammation and examples

Answer 10

• cytokines: Th1 vs. Th2; TNFa vs. IFNy vs. IL-1B

- Types of cells: neutrophils vs. eosinophils; T cells vs. B cells

Question 11

Describe what is seen in acute vs. chronic inflammation

Answer 11

Acute: granulocytes predominant, usually neutrophils; followed by macrophages; phagocytic response to clean up and kill the acute insult
-Edema, neutrophils, then macrophages

Chronic: macrophage and lymphocyte predominant (lymphohistiocytic infiltrate); attempt to deal with inadequate clearance on insult by the acute response

Question 12

4 patterns of acute inflammation

Answer 12

1. Fibrinous
2. Purulent
3. Serous
4. Ulcerative

Question 13

Fibrinous Inflammation and example of where it occurs

Answer 13

• inflammation resulting in a large increase in vascular permeability allows fibrin to pass through the blood vessels
• fibrinous pericarditis

Question 14

Purulent inflammation

Answer 14

• inflammation resulting in large amount of pus, which consists of neutrophils, dead cells, and fluid
• Infection by pyogenic bacteria such as staph is characteristic of this kind of inflammation
• abscesses

Question 15

What is an abscess?

Answer 15

• large, localized collections of pus enclosed by surrounding tissues
• purulent inflammation

Question 16

Serous inflammation and common example

Answer 16

• characterized by copious effusion of non-viscous serous fluid, commonly produced by mesothelial cells of serous membranes, but may be derived from blood plasma
• skin blisters are example

Question 17

Describe the histology of a skin blister

Answer 17

• serous inflammation

- epidermis has separated from dermis due to serous effusion

Question 18

Ulcerative inflammation

Answer 18

-inflammation occurring near an epithelium

Question 19

Ulcerative inflammation

Answer 19

• inflammation occurring near an epithelium can result in the necrotic loss of tissue from the surface, exposing lower layers
• the subsequent excavation in the epithelium is known as an ulcer

Question 20

3 histologic characteristics of chronic inflammation

Answer 20

1. collection of chronic inflammatory cells: lymphocytes
2. destruction of parenchyma
3. replacement of tissue by connect tissue–fibrosis** why tissues will not return back to full capacity

Question 21

Granulomatous inflammation

Answer 21

• special pattern of chronic tissue inflammation
• characterized by formation of granulomas, which are the result of a limited but diverse number of diseases, which include among others TB, leprosy, sarcoidosis, and syphilis
• maintained by TNFa
• giant cells common: large, multi-nucleated marcophages in horse-shoe shaped pattern

Question 22

Granulomas are often maintained by what cytokine?

Answer 22

-TNFa

Question 23

Sarcoid vs TB granulomas

Answer 23

• sarcoid: non-caseating

- TB: caseating

Question 24

Outcomes of acute inflammation

Answer 24

1. healthy resolution
2. progression to abscess and fibrosis (scarring)
3. Fibrosis right away
4. progress to chronic inflammation and then fibrosis

Question 25

What are acute phase reactants?

Answer 25

- proteins made usually by the liver in response to systemic inflammation - provide useful clinical marker for inflammation

Question 26

Acute phase reactants can be indirectly measured by __________. What is this? What is the main agent of this phenomenon?

Answer 26

- Erythrocyte Sedimentation Rate (ESR) - red blood cells form aggregates (rouleaux) in the presence of acute phase reactants (particularly fibrinogen) - rouleaux fall faster under gravity compared to free standing RBCs - if sedimentation rate is >20, probably have some inflammation

Question 27

What causes an ESR fakeout?

Answer 27

- a patient has severe inflammation, due to cytokine storm, and part of the pathophysiologic response to this is the consumption of fibrinogen - don't see rouleaux formation - can be helpful do determine infection type though, some are associated with this

Question 28

What is an amyloid and what is it caused by? How can one see them?

Answer 28

- prolonged exposure to acute phase reactants (specifically serum amyloid A---chronic inflammation) can cause large globs of protein to deposit in tissues - these disrupt function of tissues and can ultimately lead to organ failure - seen microscopically by looking for "apple-green birefringence" on a Congo Red stain

Question 29

2 types of immune therapy

Answer 29

- immunosuppressives (need less inflammation) | - immune boosters (where increased inflammation can resolve injury)

Question 30

4 types of immunosuppressives

Answer 30

1. Glucocorticoids: alter nuclear transcription and reduces leukocyte number and function (multiple, potentially severe side effects) 2. Cyclosporin A: inhibits calcineurin signaling, effectively blocking IL-2 and T-cell functions 3. Cytotoxics: giving chemotherapy to kill immune cells 4. Biologics: recombinant proteins or antibodies against specific cytokines, ligands, or receptors

Question 31

4 kinds of immune boosters

Answer 31

1. Imiquimod: TLR7 ligand useful for tx of certain epithelial cancer and viral warts (TLR agonist) 2. IFNa/IFNy: used to tx chronic viral infections and for certain immunodeficiencies 3. IVIG: passive immunization with other's antibodies 4. Vaccines: stimulate adaptive immune response against an antigen (infections, cancer)