3 - Inflammation and Repair

Question 1

What is the purpose of inflammation?

Answer 1

To bring cells and molecules of host defense from the circulation to a site of tissue damage to remove the offending agents.

Question 2

What are the two main participants in inflammation?

Answer 2

Blood vessels and leukocytes

Question 3

Do leukocytes have short or long life spans in tissues?

Answer 3

Short

Question 4

What are the cardinal signs and symptoms of inflammation?

Answer 4

Rubor (redness), calor (heat), tumor (swelling), dolor (pain), functio laesa (loss of function)

Question 5

What family of receptors senses the presence of foreign microbes?

Answer 5

Toll-like receptors (also, circulating antibodies and complement)

Question 6

Intracellular sensors can sense what molecules that indicate possible damage to the cell?

Answer 6

ATP (indicating mitochondrial leakage), low potassium (indicating cellular leakage), uric acid (indicating DNA breakdown), DNA (indicating nuclear leakage)

Question 7

Damage sensors in the cell trigger the formation of what structure?

Answer 7

The inflammasome

Question 8

What does the inflammasome produce?

Answer 8

Interleukin-1

Question 9

What are the general steps of inflammation?

Answer 9

(1) Recognition of the injurious agent, (2) recruitment of leukocytes, (3) removal of the agent, (4) regulation of the response, (5) resolution and repair

Question 10

What are the three major components of acute inflammation?

Answer 10

Dilation of small blood vessels, increased permeability of the microvasculature, migration of the leukocytes to the damaged tissues

Question 11

Why do blood vessels dilate in inflammatory situations?

Answer 11

To increase blood flow to the area and slow down the blood flow

Question 12

What is the principle inflammatory mediator leading to vasodilation?

Answer 12

Histamine (and also kinins)

Question 13

What do endothelial cells increase expression of during the inflammatory response?

Answer 13

Adhesion molecules (for leukocyte attachment)

Question 14

What is the most common method increased vascular permeability? What are other methods?

Answer 14

Endothelial cell shrinkage (increasing the interendothelial space); direct endothelial damage and necrosis, vascular endothelial growth factor

Question 15

What vessels proliferate during inflammatory responses?

Answer 15

Blood and lymph vessels

Question 16

Define lymphangitis. Define lymphadenitis.

Answer 16

Lymph vessel inflammation; lymph node inflammation

Question 17

What is the cause of the red streaks seen coming from an infected wound?

Answer 17

Lymphangitis

Question 18

What are the three steps of leukocyte migration in the blood vessel lumen?

Answer 18

Margination, rolling, and adhesion (all to activated endothelium)

Question 19

What adhesion molecules assist leukocytes in the rolling phase?

Answer 19

Selectins

Question 20

What adhesion molecules assist leukocytes in the adhesion phase?

Answer 20

Integrins

Question 21

What is the name of the process by which leukocytes leave the blood vessel? What molecules assist in this process?

Answer 21

Diapedesis (also known as transmigration); PECAM-1 and CD31

Question 22

When does chemotaxis occur?

Answer 22

After diapedesis when a leukocyte has entered the tissue space

Question 23

What are the three principal chemokines involved in chemotaxis?

Answer 23

Interleukin-8, C5a, and leukotriene B4

Question 24

What is the first responder in acute inflammation? What leukocyte will replace the first responder within 24-48 hours?

Answer 24

Neutrophils (more abundant, quicker, short half-life); macrophages (less abundant, slower, longer half-life, can proliferate in tissues)

Question 25

What three drugs are especially effective in interfering with tumor necrosis factor and inhibiting harmful inflammation?

Answer 25

Etanercept, infliximab, adalimumab

Question 26

What happens to the leukocytes post-chemotaxis once they reach the site of injury?

Answer 26

(1) They recognize the offending agents (toll-like receptors); (2) they become activated and phagocytic

Question 27

What are the three steps of leukocyte phagocytosis?

Answer 27

Recognition, engulfment, and killing (or degradation)

Question 28

What leukocyte receptors identify bacteria but not host cells?

Answer 28

Mannose receptors

Question 29

What combines with the phagosome containing a phagocytosed bacteria or other agent within the leukocyte?

Answer 29

A lysosomal granule (containing reactive oxygen species and degradation enzymes)

Question 30

How are foreign microbes killed within the body?

Answer 30

Mainly reactive oxygen species (the respiratory burst within the phagolysosome)

Question 31

What type of nitric oxide synthase is implicated in ROS formation?

Answer 31

Inducible NOS (iNOS)

Question 32

What enzymes do neutrophil lysosomes contain?

Answer 32

Lysozyme, hydrolytic enzymes, myeloperoxidase, and lactoferrin

Question 33

What are neutrophil extracellular traps?

Answer 33

Fibrillar networks released by neutrophils to trap microbes and kill them with antimicrobial substances

Question 34

What substances are released to limit and end inflammation?

Answer 34

Lipoxins, transforming growth factor-beta, interleukin-10

Question 35

What are some of the principal mediators of inflammation?

Answer 35

Vasoactive amines (e.g. histamine and serotonin), prostaglandins, leukotrienes, cytokines, and complement

Question 36

What are the sentinel cells of inflammation?

Answer 36

Mast cells, dendritic cells, macrophages

Question 37

What are the products of cyclooxygenase degradation of arachidonic acid?

Answer 37

Arachidonic acid --\> Prostaglandin G2 --\> Prostaglandin H 2--\> Prostacyclin (prostaglandin I2) + Thromboxane A2 + Prostaglandins D2 and E2

Question 38

What are the products of 5-lipooxygenase degradation of arachidonic acid?

Answer 38

Hydroperoxide (5-HPETE) --\> Leukotriene A4 --\> Leukotriene B4 + C4 + D4 + E4 AND Hydroperoxide (5-HPETE) --\> Lipoxin A4 + B4 (antiinflammatory)

Question 39

Why do COX-2 inhibitors increase the risk of adverse cardiovascular events?

Answer 39

They inhibit prostacyclin formation but leave thromboxane A2 formation untouched

Question 40

What benefits do COX-2 inhibitors show?

Answer 40

Decreased renal and gastrointestinal damage

Question 41

Of which molecules do corticosteroids decrease gene expression?

Answer 41

COX-2, phospholipase A2, iNOS, interleukin-1, TNF

Question 42

What are the principal types of exudate?

Answer 42

Serous, purulent, fibrinous

Question 43

Define ulcer.

Answer 43

An ulcer is a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue

Question 44

What are the potential outcomes of acute inflammation?

Answer 44

Resolution, fibrosis, and progression to chronic inflammation

Question 45

How long does chronic inflammation last?

Answer 45

Weeks to months

Question 46

What processes coexist in chronic inflammation?

Answer 46

Inflammation, tissue damage, and tissue repair

Question 47

What are some causes of chronic inflammation?

Answer 47

Persistent infections, hypersensitivity disorders, prolonged exposure to toxic agents

Question 48

What morphological changes characterize chronic inflammation?

Answer 48

Mononuclear cell infiltrate (macrophages and lymphocytes), tissue destruction, attempts at tissue healing (angiogenesis and fibrosis)

Question 49

Which cell is the major actor in chronic inflammation?

Answer 49

The macrophage

Question 50

What does classical activation cause macrophages to do? What does the alternative activation cause macrophages to do?

Answer 50

Microbicide; tissue repair

Question 51

What is granulomatous inflammation? What is its purpose as a form of chronic inflammation?

Answer 51

Granulomatous inflammation is a form of chronic inflammation characterized by collections of activated macrophages, often with T lymphocytes, and sometimes associated with central necrosis; a cellular attempt to contain an offending agent that is difficult to eradicate.

Question 52

What are the two types of macrophages seen in granulomas?

Answer 52

The activated macrophages may develop abundant cytoplasm and begin to resemble epithelial cells and are called epithelioid cells. Some activated macrophages may fuse, forming multinucleate giant cells.

Question 53

What are the two main types of granuloma?

Answer 53

Foreign body granulomas and immune granulomas

Question 54

What is a foreign body granuloma?

Answer 54

Typically, foreign body granulomas form around materials such as talc (associated with intravenous drug abuse), sutures, or other fibers that are large enough to preclude phagocytosis by a macrophage and do not incite any specific inflammatory or immune response.

Question 55

What is an immune granuloma?

Answer 55

Immune granulomas are caused by a variety of agents that are capable of inducing a persistent T cell-mediated immune response.

Question 56

What is the name of the collective signs and symptoms of the systemic effects of inflammation?

Answer 56

The acute-phase response

Question 57

Which cytokines are the principal mediators of the acute-phase response (systemic effects of inflammation)?

Answer 57

TNF, IL-1, IL-6, interferons

Question 58

What are the principal effects of the acute-phase response (systemic effects of inflammation)?

Answer 58

Fever, C-reactive protein, leukocytosis, and (in severe cases), septic shock

Question 59

What family of factors causes proliferation of hematopoietic stem cells in the bone marrow?

Answer 59

Colony-stimulating factors

Question 60

Which parenchymal organ has remarkable regenerative capacity? It can grow back after loss of what percentage of its cells?

Answer 60

The liver; 90%

Question 61

Which parenchymal organs have partial regenerative capacity?

Answer 61

The lungs, adrenal glands, thyroid, and pancreas

Question 62

How does the liver regenerate?

Answer 62

The proliferation of remaining hepatocytes and the regeneration from progenitor cells

Question 63

What are the steps of scar formation?

Answer 63

Angiogenesis, granulation tissue formation, remodeling of the scar tissue

Question 64

What role do macrophages play in tissue repair?

Answer 64

They phagocytize debris from the wound and secrete growth factors and cytokines to promote tissue growth

Question 65

Describe the process of angiogenesis.

Answer 65

Question 66

How is new connective tissue deposited in scar formation?

Answer 66

Fibroblasts migrate to the area and release ECM (transforming growth factor-beta is the most important cytokine in this process)

Question 67

Define healing by first intention (or primary union).

Answer 67

Healing when the injury involves only the epithelial layer One of the simplest examples of this type of wound repair is the healing of a clean, uninfected surgical incision approximated by surgical sutures.

Question 68

Define healing by second intention (or secondary union).

Answer 68

When cell or tissue loss is more extensive, such as in large wounds, abscesses, ulceration, and ischemic necrosis (infarction) in parenchymal organs, the repair process involves a combination of regeneration and scarring.

Question 69

Carefully sutured wounds have what percentage of the strength of normal skin?

Answer 69

~70%

Question 70

After suture removal (1 week later), what percentage of the strength of unwounded skin does the healing skin have?

Answer 70

10%

Question 71

What percentage of unwounded skin strength does the healing skin have after 3 months?

Answer 71

70-80% (there will likely be no substantial improvement beyond that)

Question 72

What is the condition of an organ upon excessive deposition of collagen and scar tissue?

Answer 72

Fibrosis

Question 73

If a scar is raised due to excess collagen deposition, what is it called?

Answer 73

A hypertrophic scar

Question 74

If a scar grows outside the boundaries of a wound and does not regress, what is it called?

Answer 74

A keloid (more common in African-American patients)

Question 75

What is it called when excessive granulation tissue is deposited and it rises above the skin (disrupting reepithelialization)?

Answer 75

Exuberant granulation (must be removed by cautery or surgery to allow skin healing)

Question 76

Although contraction is an important part of the healing process, what is an excessive amount if contraction called? (often seen in burn patients)

Answer 76

A contracture

Question 77

What are two types of complication in wound healing when insufficient granulation or scar tissue is laid down?

Answer 77

Dehiscence (wound rupture) or ulceration