Module 1 -Path Continued

Question 1

What are the five cardinal signs in inflammation?

Answer 1

Redness (histamine and vasodilation)
Hot (vasodilation) 
Pain (bradykinin) 
Swelling (histamine/vasodilation) 
Loss of Function

Question 2

What are the steps in acute inflammation?

Answer 2

Transient vasoconstriction (neurogenic) –> vasodilation (via histamine) –> increased vascular permeability/exudation (margination (rouleaux formation of RBCs pushes WBCs to periphery) –> rolling (mediated by selectins P and E) –> adhesion/emigration via integrins (ICAM-1 and VCAM) —>after this diapedisis or transmigration (movement of WBC from vessels to interstitial space)

Question 3

What are the chemotactic factors for PMNs/neutrophils?

Answer 3

C5a (most important) 
Bacterial Products (most important for macrophages) 
Arachidonic Acid Metabolites (Leukotriene B4) 
Cytokine --> IL-8

Question 4

What are the chemotactic factors for macrophages?

Answer 4

MCP1 (CCL-2) , dead neutrophils and bacterial products

Question 5

Acute Inflammation vs Acute Congestion, which is transudate and which is exudate?

Answer 5

Acute Inflammation = Exudate

Acute Congestion = Transudate

Question 6

What are features of exudate fluid?

Answer 6

high proteins, white cells and specific gravity

Question 7

What forces drive the formation of a transudate?

Answer 7

Hydrostatic pressure

Question 8

What are the four chemical mediators of fever?

Answer 8

Thromoboxane
PGE2
TNFalpha
IL1

Question 9

For any viral infection, if they ask what is the first inflammatory cell on site, what is it?

Answer 9

CD8 lymphocytes

EBV, MONO, HPV, Etc

Question 10

For any bacterial infection or coagulative necrosis, what cells are there first?

Answer 10

Neutrophils

Question 11

What is the process of phagocytosis?

Answer 11

1. Recognition and Attachment –> coated with opsonins (IgG and C3b)
2. Engulfment –> formation of phagolysome requires presence of Ca2+ and Mg2+
3. Killing/Degradation –>
   -O2 dependent mechanisms: H2O2-myeloperoxidase-halide system
   and MPO independent killing (most potent radial OH)
   –O2 independent mechanisms: decreased pH due to lactic acid

Question 12

What are the 4 types of inflammation?

Answer 12

Serous –> Albumin containing exudate; seen in blister, pulmonary TB
Fibrinous –> contains Fibrin; seen in rheumatic fever (bread and butter pericarditis)
Suppurative/purulent –> liquefactive necrosis caused by pyogens (pus w/neutrophils); seen in acute appendicitis
Sanguinous –> contains large number of RBCs; tumor invasion

Question 13

What are the changes in vascular permeability in acute inflammation?

Answer 13

Increased intravascular hydrostatic pressure (vasodilation) or decreased intravascular osmotic pressure (decreased albumin) –> increase interstitial fluid (edema)

Question 14

What are the steps in vascular permeability?

Answer 14

1. Endothelial Cell Contraction-> histamine in venules —> immediate transient response
2. Junctional Contraction –>Cytokine mediated (TNF and IL-1)
3. Direct Endothelial Injury –> Endothelial detachment in capillaries and venules; immediate sustained response
4. Leukocyte dependent Endothelial Injury –> inflammatory cells release ROS causing endothelial detachment in venules and pulmonary capillaries
5. Increased Transcytosis –> in prescence of VEGF –> increased permeability

Question 15

What are the cell derived mediators of increased vascular permeability?

Answer 15

Arachidonic Acid Metabolites –> derived from cell membrane phospholipids

• Prostaglandins: vasodilation and increased permeability
• Leukotrienes: increased permeability and chemotactic activity
• PAF-vasodilation, increased permeability and chemotactic activity
• Amines: vasodilation and increased permeability (venules only) (includes histamine and sertonin)
• Endothelins: powerful vasoconstrictors

Question 16

What are the plasma derived mediators of increased vascular permeability?

Answer 16

Kinins and coagulation cascade: bradykinin (vasodilation, vascular permeability and pain)
Clotting system: prevents infection spread, end product = fibrin
Complement system: opsinizing bacteria=C3b; attracting leukocytes (Chemotaxis)=C5b, 6,7 complex and C5a; mast cell activators = degranulation and histamine release= C3a, C5a; C6-C9=create pores in bacterial walls

Question 17

Chronic Inflammation, what is an example?

Answer 17

Peptic Ulcer

Question 18

What is the pathogenesis for chronic inflammation?

Answer 18

Previous acute inflammation (>/= 2 weeks)

De Novo: Granulomatous Inflammation (TB) and autoimmune disease

Question 19

What the main cells for bacterial chronic inflammation?

Answer 19

CD4 T cells Monocytes and Macrophages, lymphocytes, plasma cells, fibroblasts and endothelial cells

Question 20

What is the hallmark of chronic inflammation?

Answer 20

Hallmark = fibrosis by fibroblasts leading to loss of function
PMNs (neutrophils) are absent

Question 21

What is the presentation for chronic inflammation?

Answer 21

No pain normally because no more bradykinin, but every chronic inflammation can have an episode of acute on chronic inflammation which does cause pain
(happens alot in crohns, RA, gout and psoriasis)

Question 22

What has to be secreted in order to get fibroblasts?

Answer 22

TGFbeta

Question 23

In chronic inflammation, collagen is initially type III and with blood vessels and angiogensis and this forms granulation tissue. how long does it take to form granulation tissue?

Answer 23

2 weeks

Question 24

In chronic inflammation how long does it take for collagen to get transformed from type III to type I ?

Answer 24

2 months process called cicratization (which means scaring)

Question 25

In acute on chronic flare, what cells would you see?

Answer 25

PMNs (because this is a flare) and you would see all the signs of acute inflammation as well

Question 26

is there pain with chronic inflammation?

Answer 26

nope just loss of function

Question 27

In the picture of the intestine for peptic ulcer, what is the white stuff, red and dark red?

Answer 27

White stuff --> fibrosis Red --> chronic inflammation Dark red --> acute flare

Question 28

What type of collagen is a keloid?

Answer 28

type III (thats why keloid looks super soft)

Question 29

What type of collagen in a hypertrophied scar?

Answer 29

type I

Question 30

In regards to caseating granuloma, how is the central area of caseous necrosis formed?

Answer 30

No nuclei in center -> walled off by chronic inflammatory cells (macrophages, T cells, plasma cells, fibroblast, giant cells, epitheloid cells but no PMNs)

Question 31

What are examples of non-caseating granulomas?

Answer 31

no central area of necrosis | Crohns, Sarcoidosi and Berylliosis

Question 32

What are examples of pyogenic/suppurative granulomas?

Answer 32

purulent (has PMNs/neutrophils) granulomas | Cat Scratch Disease and Lymphogranuloma Venterum (LGV) --> STI caused by chlamydia

Question 33

What are examples of foreign body granuloma?

Answer 33

Gout (monosodium uric acid crystals) and foreign body giant cells