Inflammation 1

Question 1

INFLAMMATION

Answer 1

It is a complex reaction to injurious agents such as microbes and trauma, as well as to damaged, usually necrotic cells ( dead cells ). It consists of vascular responses, migration and activation of leukocytes ( white blood cells ), and systemic reactions (such as fever)

Question 2

DESIRABLE EFFECTS OF INFLAMMATION on foreign agents and tissues

Answer 2

A. inactivation and elimination of offending agents
B. demolition of necrotic ( dead ) tissues
C. establishing conditions for repair and restoration

Question 3

Acute inflammation example

Answer 3

asthma (associated with inflammation of airways)

Question 4

Chronic inflammation examples

Answer 4

1. rheumatoid arthritis: chronic inflammation of joints causing severe joint destruction, deformities and disability
2. atherosclerosis- inflammation is an important factor causing chronic injury to arterial walls with resulting wall thickening (may lead to decreased blood flow)

Question 5

WHITE BLOOD CELLS IN THE INFLAMMATORY RESPONSE

Answer 5

GRANULOCYTES: NEUTROPHILS, EOSINOPHILS, BASOPHILS
MONOCYTES
LYMPHOCYTES

Question 6

NEUTROPHILS

Answer 6

a. also called: polymorphonuclear leukocytes or “polys” because their nuclei have variably appearing lobes; segmented neutrophils or “segs” because nuclei have distinct lobes or segments
b. dominate acute inflammatory response; are 1st to arrive at the “ scene”

c. capable of amoeboid motion, phagocytosis ( engulfment )
of offenders, and intracellular killing of offenders

d. digest necrotic tissue (e.g. by releasing enzymes): an example is digesting necrotic heart muscle after heart attack ( myocardial infarction ) has occurred so tissue repair can occur

Question 7

EOSINOPHILS

Answer 7

a. have large, red granules ( contain major basic protein which is toxic to parasites )
b. important in allergic reactions and parasitic infections

Question 8

BASOPHILS

Answer 8

a. have large, deep blue granules which contain histamine
b. normally exist in small #s in acute inflammatory response
c. mast cells are in tissue and are very similar to basophils; they release histamine during acute inflammatory response (and are more important than basophils in the acute inflammatory response)
d. mast cells are located in numerous locations: skin; mucosa of GI and respiratory tracts; by blood vessels; and by nerves

Question 9

Monocytes

Answer 9

1. monocytes circulate in blood, and transform in tissue into macrophages
2. macrophages phagocytose invaders
   a. can kill invaders intracellularly
   b. can stimulate lymphocytes to participate in inflammatory response
3. macrophages arrive at acute inflammatory site later
   than neutrophils ( they phagocytose dead neutrophils and “clean up” the site ): critical for resolution of inflammation
4. macrophages dominate chronic inflammation, because:
   a. they can undergo cell division and accumulate at the site
   b. release products which promote the coexistence of inflammation, tissue destruction and tissue fibrosis
   ( neutrophils do not undergo cell division, so are not typically important in chronic inflammation )
5. are central in repair of injured tissue (wound healing)

Question 10

LYMPHOCYTES

Answer 10

small, round cells with little cytoplasm
1. small #s in acute inflammatory response except with certain
infectious agents:
a. certain viruses ( e.g. Epstein- Barr virus: infectious mononucleosis )
b. pertussis ( whooping cough; caused by a bacteria )
2. important in chronic inflammation

Question 11

ACUTE INFLAMMATION

Answer 11

• the immediate and early response to an injurious agent

- involves accumulation of fluid and white blood cells (WBC) at injury site

Question 12

ACUTE INFLAMMATION - VASCULAR EVENTS

Answer 12

changes in microcirculation
1. vasodilation: results in increased blood flow and filling of capillary with blood (congestion)
2. increased vascular permeability: increased leakiness of vessels allows proteins to pass through them→decreased intravascular proteins
3. outflow of fluid into extravascular space- results from:
a. increased vascular permeability
b. decreased intravascular proteins results in decreased intravascular oncotic pressure (also called colloid osmotic pressure)→ water leaves vessel
(oncotic pressure normally helps keep water in vessels )
c. increased hydrostatic pressure in vessels due to increased blood flow ( intravascular hydrostatic pressure normally pushes water out of vessels )
d. fluid in extravascular space is called edema fluid

Question 13

ACUTE INFLAMMATION - CELLULAR EVENTS

Answer 13

fluid which is high in protein and white blood cell content accumulates at injury site

NEUTROPHILS PREDOMINATE AT INJURY SITE (acute inflammatory site) during 1st 6-24 HOURS, THEN MACROPHAGES ARRIVE AT INJURY SITE

both neutrophils and macrophages phagocytose invaders ( e.g. bacteria ) or foreign material in an amoeboid fashion, and kill the invaders intracellularly

STEPS of PHAGOCYTOSIS and intracellular KILLING of INVADER
1. recognition of and binding of invader to phagocytic cell: aided by antibodies and complement proteins

2. engulfment of invader and formation of intracellular vacuole (phagosome)

Question 14

CLINICAL SIGNS OF INFLAMMATION

Answer 14

A. rubor ( redness ): caused by vasodilation and congestion→increased blood flow

B. calor ( heat ): caused by increased blood flow ( apparent with skin; not
internal body structures that are normally warmer than skin )

C. tumor ( swelling ): caused by outflow of fluid into extravascular space within interstitium (space between cells); accumulation of fluid is called edema
D. dolor ( pain ): caused by local pressure from swelling and chemical mediators ( bradykinin and prostaglandins- to be discussed )

E. Virchow later added a fifth clinical sign in 19th century: functio laesa (loss of function)

Question 15

CELL DERIVED MEDIATORS IN THE INFLAMMATORY RESPONSE

Answer 15

HISTAMINE
ARACHIDONIC AND ACID METABOLITES
CYTOKINES

Question 16

PLASMA DERIVED MEDIATORS IN THE INFLAMMATORY RESPONSE

Answer 16

COMPLEMENT AND KININ SYSTEMS

Question 17

HISTAMINE

Answer 17

very important in earliest inflammatory response
1. causes vasodilation and increased vascular permeability

2. mast cells are similar to basophils, but are not derived from blood basophils (as tissue macrophage are derived from monocytes); mast cells are a very important source of histamine
3. release of histamine from mast cells is triggered by:
   type I hypersensitivity reaction; physical injury; other chemical mediators (e.g. complement proteins- to be discussed)

anti-histamine drugs can treat inflammation e.g. Benadryl; Claritin (especially when associated with an allergic condition)

Question 18

ARACHIDONIC AND ACID METABOLITES

Answer 18

arachidonic acid is released from phospholipids in cell membranes by phospholipase A2 )

glucocorticoid drugs mediate anti-inflammatory actions in part by blocking this important step ( and preventing production of arachidonic acid metabolites )

        the production of arachidonic acid metabolites involves 2 major pathways:

PATHWAY REQUIRING CYCLOOXYGENASE ENZYME:
results in production of various prostaglandins
effects of prostaglandins: vasodilation; pain; fever

non-steroidal anti-inflammatory drugs (NSAID) and aspirin inhibit cyclooxygenase and block production of prostaglandins: they are therefore useful in treating inflammation and associated symptoms brought about by prostaglandins ( pain; fever)

examples of NSAID: naproxen (Aleve-over the counter ); ibuprofen ( Advil-over the counter )

PATHWAY REQUIRING LIPOOXYGENASE ENZYME:
results in the production of leukotrienes

effects of leukotrienes:
increased vascular permeability; leukocyte chemotaxis; constriction of bronchial passages ( bronchospasm )
IMPORTANT IN BRINGING ABOUT SIGNS AND SYMPTOMS OF ASTHMA

Leukotriene inhibitor is used to treat asthma:
Singulair ( brand name ); montelukast sodium ( generic )- causes inhibition of airway leukotriene receptors

Question 19

COMPLEMENT SYSTEM PROTEIN PRODUCTS AND THE ROLE THEY PLAY IN THE INFLAMMATORY PROCESS

Answer 19

1. vasodilation and increased vascular permeability
   (brought about by stimulating release of histamine from mast cells)
2. promote phagocytosis of invaders by aiding with binding of invader to phagocytic cells (macrophages and neutrophils)
3. directly kill invader cells by membrane attack complex (MAC)
4. recruit white blood cells ( WBC) to site of inflammation

Question 20

KININ SYSTEM PROTEIN PRODUCTS AND THE ROLE THEY PLAY IN THE INFLAMMATORY PROCESS

Answer 20

1. bradykinin = important product
2. actions: increases vascular permeability; vasodilation;
   pain

Question 21

LYMPHATICS

Answer 21

delicate channels draining distally to proximally to return extravascular fluid to venous system ( drain from far to nearer parts of body )

bring microbial agents escaping 1st line of defense (innate immunity e.g. skin; natural killer cells; neutrophils) to lymph nodes (2nd line of defense)

resolution of inflammation (to be discussed)

a. drain fluid from extravascular space ( edema )
b. remove leukocytes and cell debris

Question 22

LYMPH NODES

Answer 22

discrete structures with a capsule that have macrophages and lymphocytes; located in clusters in various areas of body: examples- cervical, axillary, inguinal, pelvic, iliac, mesenteric, and mediastinal lymph nodes

filter out microbial agents (e.g. are phagocytosed by macrophages)

sites where lymphocytes bind with antigens of microbial agents, are activated, and participate in immune defense: e.g. B lymphocytes transform into plasma cells and make antibodies which will help fight invaders

Question 23

LYMPHNGITIS

Answer 23

secondary inflammation of lymphatic channels draining infectious organisms

example: infection of hand ( e.g. from human, dog, cat, or insect bite ) spreads up arm through lymphatic channels and is visible as red streaks on the arm ( primary site of infection on hand has signs of inflammation and is called cellulitis )

Question 24

LYMPHADENITIS

Answer 24

secondary inflammation and infection of lymph nodes draining a site of bacterial infection
example: bacterial infection of tonsils can spread to tonsillar lymph node (located in neck at angle of mandible)

Question 25

POSSIBLE OUTCOMES OF ACUTE INFLAMMATION

Answer 25

A. Complete Resolution: restoration of tissue to normal histology and function 1. lymphatics and macrophages are the “ clean up crew” that “mop up” the extravascular fluid (edema), necrotic tissue, and leukocytes 2. no more leukocytes are recruited, and inflammation subsides 3. tissue injured is capable of regeneration ( replacement of lost cells with cells similar in structure and function )- regenerative capacities of cells to be discussed in wound healing lecture B. Abscess Formation (to be discussed in inflammation II lecture) C. Healing by Scarring (to be discussed in wound healing lecture) D. Progression to Chronic Inflammation NOTE: inflammation sometimes may begin as that associated with chronic inflammation- to be discussed ( rather than be a progression from acute inflammation )- it depends on the initial injurious stimulus e.g. autoimmune disease ( rheumatoid arthritis ); tuberculosis

Question 26

SETTINGS IN WHICH CHRONIC INFLAMMATION ARISES

Answer 26

A. persistent infection by certain microorganisms - examples 1. bacteria causing tuberculosis and syphilis 2. certain viruses (e.g. those causing hepatitis B and C) 3. fungi and parasites organisms often difficult to rid body of; some may have a poorly degradable component B. prolonged exposure to potentially toxic agents example: silicosis 1. caused by chronic occupational exposure to silica ( e.g. coal miners; sandblasters ) 2. is a slowly progressive, scarring lung disease 3. is most prevalent chronic occupation- associated disease in world C. chronic autoimmune disease (there are many) patient’s immune system causes inflammation involving his/her own tissues resulting in tissue injury examples: rheumatoid arthritis; systemic lupus erythematosus

Question 27

CELLS PRESENT IN CHRONIC INFLAMMATION

Answer 27

MACROPHAGES AND LYMPHOCYTES

Question 28

MACROPHAGES IN CHRONIC INFLAMMATION

Answer 28

1. are activated by bacterial toxins and cytokines ( messenger proteins ) produced by helper T lymphocytes 2. when activated, can produce an impressive number of chemical mediators which have the following effects: a. recruitment of leukocytes (white blood cells) to inflammatory site: this maintains active inflammation b. tissue destruction ( from toxic oxygen metabolites, proteases, and nitric oxide ) c. scarring: stimulation of fibroblast proliferation and collagen production ( to be covered in wound healing lecture )

Question 29

LYMPHOCYTES IN CHRONIC INFLAMMATION

Answer 29

lymphocytes can aid in killing of invaders: 1. B lymphocytes or “B cells” participate in humoral immunity: activated B cells (plasma cells) produce antibodies functions of antibodies: “bind and block” a. bind to attachment sites on viruses to block their infection of host cells b bind attachment sites on bacteria to block attachment to host tissue (e.g. in GI tract) c. bind and block toxins “bind and connect” a. connect microbial organism to neutrophils or macrophage to aid with phagocytosis b. connect microbial antigen with complement protein to activate complement 2. T lymphocytes or “T cells” participate in cell mediated immunity a. directed against fungi, viruses, Mycobacterium tuberculosis ( bacteria which cause tuberculosis ), and cancer cells b. cytotoxic T cells kill infected cells and cancer cells c. helper T cells regulate actions of B cells, cytotoxic T cells, and macrophages

Question 30

DEFINE GRANULOMATOUS INFLAMMATION

Answer 30

specific type of chronic inflammatory reaction characterized by: 1. a sheet of activated macrophages with pink cytoplasm ( called epithelioid cells ) 2. multinucleated giant cells ( fused epithelioid cells ) 3. “collar” of T lymphocytes which surround the macrophages (T lymphocytes release cytokines to activate the macrophages and propagate the inflammation) macrophages are activated by poorly degradable microbes and foreign material that are difficult to rid from body; activated macrophages surround and contain them

Question 31

PATHOLOGIC CONDITIONS IN WHICH GRANULOMATOUS INFLAMMATION IS PRESENT

Answer 31

1. foreign body granulomas a. irritants which cannot be phagocytosed ( e.g. sutures) b. epithelioid cells ( activated macrophages ) and giant cells surround foreign body, without much T cell involvement 2. immune granulomas: (T cell involvement important ) a. microorganisms which are poorly degradable and are very difficult for phagocytic cells to kill (e.g. mycolic acid of tuberculous bacteria cannot be degraded by enzyme) examples are microbes which cause tuberculosis, syphilis, and cat scratch disease b. sarcoidosis is a systemic granulomatous disease of unknown cause ( granulomas located in various tissues )