Products of acute inflammation

Question 1

Fluidic phase

Answer 1

Dilute and localize the stimulus

• increased blood flow –> mediators (histamine from mast cells and platelets) –> vasodilation of arterioles = opening of capillary beds = increased blood flow = head and redness (erythema)
• increased permeability of capillaries and postcapillary venules –> loss of fluid and increased vessel diameter –> slower blood flow, concentration of RBCs and increased blood viscosity = swelling

Question 2

Retraction of endothelial cells

Answer 2

Occurs mainly in venules (high density of histamine receptors)

• induced by histamine, NO, etc
• rapid and short lived (minutes)
• retraction by contraction of actin/myosin filaments or reorganization of the cytoskeletal microtubule and proteins

Question 3

Endothelial injury

Answer 3

Occurs in arterioles, capillaries, venules
- caused by burns, microbial toxins
- rapid, may be long lived (hours to days)
= endothelial cell necrosis and detachment
- activates clotting and complement

Question 4

Serous fluid

Answer 4

Clear watery fluid, low concentration of plasma protein with no or low number of leukocytes (transudate)

• results from increased vascular permeability, suggests injury is mild or peracute
• may become cellular or rapidly resorbed by lymphatic drainage
• mild skin injury, allergies, serosal surfaces
• affected tissues spread apart by watery fluid

Question 5

Fibrinous inflammation

Answer 5

Pattern of acute inflammation

• caused by infectious agents
• accumulation of fluid with a high concentration of plasma protein (can have high or low cellularity depending on duration/stimulus) = exudate
• leakage of large molecular weight proteins (fibrinogen!!!)
• fibrinogen polymerizes to form fibrin

Question 6

Fibrinous exudate

Answer 6

Often in serous membranes of body cavities

Question 7

Gross characteristics of fibrinous exudates

Answer 7

• surface of affected tissue is red (hyperemic)
• surface may be granular or dull
• covered with thick, stringy, white gray to yellow material that is easily removed

Question 8

Microscopic characteristics of fibrinous exudates

Answer 8

Eosinophilic proteinaceous material: fibrillary, along with edema
- rapidly becomes infiltrated by neutrophils = fibrinosuppurative exudate

Question 9

Consequence of fibrinous inflammation

Answer 9

May resolve without any sequelae

- if extensive, fibroblasts may migrate in and begin organizing exudate = fibrous adhesions

Question 10

Cellular phase

Answer 10

Delivers leukocytes to the site in order to kill and digest stimulus (neutrophils and macrophages)
- activated leukocytes cause tissue damage and prolong inflammation

Question 11

Leukocyte adhesion cascade

Answer 11

Movement of leukocytes from vessel into the connective tissue

• driven by chemokines, cytokines and chemoattractant substances
• process initiated during fluidic phase: blood stasis –> leukocytes accumulate along vascular endothelium

Question 12

Process of the cellular phase

Answer 12

• margination: leukocytes move to periphery of vascular lumen in apposition with endothelial cell (pavementing)
• rolling: leukocytes adhere transiently to endothelium
• adhesion to endothelium: firm adhesion
• migration: migration through the endothelium and then to the stimulus

Question 13

Rolling and adhesion

Answer 13

Mediated by adhesion molecules expressed on leukocytes and endothelial cells
- expression enchanced by cytokines (TNF, IL-1/6)

Question 14

Leukocyte migration through endothelium

Answer 14

Occurs mainly in post-capillary venules

• chemokines stimulate cells to migrate
• cells migrate toward stimulus due to chemical concentration gradient (chemotaxis)
• pseudopodia from leukocytes extend between endothelial cells and contact the basement membrane and extracellular matrix proteins

Question 15

Chemotaxis

Answer 15

Leukocytes move toward the site of injury

• exogenous and endogenous substances act as chemoattractants
• common exogenous: bacterial products, lipids
• common endogenous: cytokines (IL-8), components of complement system, arachidonic acid metabolites (leukotriene B4)

Question 16

Cellular infiltrate varies with _______

Answer 16

Age of response and type of stimulation

• neutrophils: 6-24 hrs
• monocytes: 24-48 hrs

Question 17

First cells to arrive depends on the stimulus

Answer 17

• neutrophils in bacterial infection
• lymphocytes and plasma cells in some hypersensitivity rxns
• eosinophils in allergic rxns
• lymphocytes in viral infection

Question 18

Purulent inflammation

Answer 18

Response consists of accumulation of fluid with high concentration of plasma protein and high number of neutrophils (exudate)

Question 19

What word is often used with purulent?

Answer 19

Suppurative

Question 20

Pus

Answer 20

Accumulation of dead neutrophils

Question 21

Plegmon

Answer 21

Pus distributed in tissue layers or along tissue layers

- cellulitis

Question 22

Gross purulent inflammation

Answer 22

Surface or CT is hyperemic with thick white to yellow material

• white: neutrophils are predominant
• yellow: lot of necrotic debris
• consistency: may be water, creamy, or firm
• odor: dependent of accompanying tissue necrosis and inciting agent

Question 23

Fibrinopurulent

Answer 23

When purulent inflammation is mixed with fibrin

Question 24

Microscopic purulent inflammation

Answer 24

Large numbers of neutrophils, many degenerate neutrophils and mixed with necrotic cellular debris, tissue debris, plasma proteins, fibrin

Question 25

Outcome of purulent inflammation

Answer 25

- neutralize - form pus = resorption of pus - may progress to chronic inflammation --> abscess: circumscribed collection of pus surrounded by CT capsule

Question 26

Are abscesses acute or chronic?

Answer 26

Chronic!!

Question 27

TNF, IL-1, IL-6 result in _______

Answer 27

Fever - mediated by prostaglandins that are increased in the hypothalamus - cytokines increase cyclooxygenases that convert AA to PGE2 - NSAIDS reduce fever by inhibiting prostaglandin synthesis

Question 28

TNF, IL-1 and IL-4

Answer 28

Increase production of leukocytes by the bone marrow - results from mobilization of neutrophils from storage pools in bone marow - increased neutrophils in the blood (neutrophilia)

Question 29

TNF

Answer 29

Energy balance | - promote lipid and protein metabolism and suppressing appetite = cachexia

Question 30

____ and ____ stimulate acute phase protein production by the liver

Answer 30

IL-1 and IL-6

Question 31

What are 3 acute phase proteins?

Answer 31

- C reactive protein* - serum amyloid A* - fibrinogen * bind to microbial cell walls and activate complement

Question 32

How can prolonged production of acute phase proteins be deterimental?

Answer 32

Secondary amyloidosis

Question 33

What are systemic effects of cytokines and acute phase proteins?

Answer 33

Affect heart rate, blood pressure and body temperature

Question 34

Septicemia

Answer 34

Significant form of bacteremia complicated by toxemia, fever, malaise, shock - multiplication of microorganisms within blood - inflammation is not controlled locally, but is systemic - widespread endothelial damage - septic shock and DIC are sequelae of advanced bacterial septicemia

Question 35

LPS

Answer 35

Bacterial endotoxins and bacterial cell wall components - gains entry from microflora of the bowl (intestinal ischemia) - activates endothelial cells and leukocytes - activates factor XII to initiate intrinsic coagulation - directly activates complement

Question 36

Clinical manifestation of LPS

Answer 36

DIC, hypotension, metabolic disturbances, multiple organ failure and death

Question 37

Gross findings of septicemia

Answer 37

Fluid in body cavity, pulmonary edema, petechial hemorrhage, congestion of liver and intestine

Question 38

Histologic findings of septicemia

Answer 38

Acute necrosis of renal tubules, centrolobular hepatocytes and cardiac myocytes