Pathology 10-12 - Inflammation

Front 1

Define: exudate

Back 1

Specific gravity > 1.02 = due to ↑ permeability

Front 2

Define: transudate

Back 2

Specific gravity < 1.02 = due to ↑ pressure

Front 3

Define: edema

Back 3

Excess interstitial fluid

Front 4

Define: pus

Back 4

Purulent exxudate - leukocytes, debris of dead cells and microbes

Front 5

Define: inflammation

Back 5

Is a complex reaction directed to injurious agents which consist of a vascular response and leukocyte involvement

Front 6

When is inflammation bad?

Back 6

Chronic inflammation - chrones, RA,

Front 7

What are the symptoms of acute inflammation

Back 7

Edema + leukocyte emigration

Front 8

What are the symptoms of chronic inflammation

Back 8

Lymphocytes + macrophages

Front 9

Define: acute inflammation

Back 9

Rapid response to injurious agent -> deliver mediators of host defense to site of injury; 3 components - 1. ↑ blood flow, 2. ↑ vascular permeability, 3. emigration of leukocytes

Front 10

MOA of a mosquito bite

Back 10

Mosquito bite -> left behind antigens ->IL-1 + TNF released -> causes mast cell disruption -> releases histamine -> swollen + red (inflammation) -> blood is laminar blood flow -> capilaries dilate -> ↓ velocity of blood -> non-laminar flow -> homogenous mixture of blood -> neutrophils(most important cell in acute inflammation) -> neutrophils start rolling -> rolls thru venules -> diapedesis -> integrins(neutrophil side) + selectins(venule endothelial cells) -> causes binding ->

Front 11

What is the function of histamine

Back 11

Vasodilation

Front 12

Venules

Back 12

↑ pore size + arterioles re dilated

Front 13

What are the pro-inflammatory cytokines

Back 13

C5a, IL-8, TNF-alpha, IL-1, PAF, E-selectins, ICAM-1

Front 14

What are the steps in chemotaxis in acute inflammation?

Back 14

1. Vasodilation, 2. ↑ permeability, 3. stasis, 4. migration, 5. rolling, 6. adhering, 7. diapedesis, 8. chemtaxis

Front 15

What are the cellular events in acute inflammation

Back 15

Ingest offending agents, kill bacteria, get rid of necrotic tissue and foreign substances

Front 16

What are the 3 selectins

Back 16

E-> endothelium, P -> endothelium + plaetlets, L -> most leukocytes

Front 17

What are the mucin-line glycoproteins

Back 17

Heparin sulfate -> serves as lignads for leukocyte adhesion molecule (CD44); on extracellular matrix and cell surfaces

Front 18

Weible-palade bodies

Back 18

Intracellular membrane bound storage organelles for von willebrands' factor(vWF)

Front 19

ESL-1

Back 19

Binds E-selectin

Front 20

PSGL-1

Back 20

Binds P-selectin

Front 21

CD11/18

Back 21

Binds ICAM-1

Front 22

L-selectins

Back 22

glyCAM

Front 23

Myeloperoxidase

Back 23

H202 -> HOCl

Front 24

Histamine

Back 24

store d inside mast cless(intracellular storage)

Front 25

How are prostaglandins and leukotrienes

Back 25

Prostaglandins + leukotrienes are made on the fly

Front 26

What are the 3 steps to phagocytosis?

Back 26

1. Recognition, 2. attachment, 3. engulfment, 4. killing, 5. degradation

Front 27

What are the chemical mediators of inflammation?

Back 27

1. Complement proteins, 2. kinins, 3. histamine, 4. de novo molecules (prostaglandins and cytokines)

Front 28

What are the vasoactive amines that are present in preformed intracellular "stores"?

Back 28

Histamine + serotonin

Front 29

What is another name for serotonin?

Back 29

5-Hydroxytryptamine (5-HT)

Front 30

What cell type releases serotonin?

Back 30

Platelets - Actions are similar to histamine -> vasodilation, ↑ vascular permeability

Front 31

What is the effect of bradykinin?

Back 31

1. ↑ vascular permeability(venules), 2. vasodilation(arterioles), 3. smooth muscle constriction, 4. pain signal!!

Front 32

What molecule is the main link between coagulation system and acute inflammation?

Back 32

Thrombin

Front 33

When initiating factor XII(aka hageman factor) what are the 4 outcomes?

Back 33

1. Clotting -> fibrin, 2. bradykinin, 3. fibrinolytic, 4. complement activation, 5. acute phase proteins

Front 34

What drugs blocks cyclooxygenase

Back 34

NSAIDS

Front 35

What is the function of COX-1 in the GI?

Back 35

COX-1 expressed in gastric mucosa + PG generated protect against acid-induced damage -> thus if u take too much asprin you are at risk for peptic ulcers

Front 36

What are the 2 pathways of eicosinoids?

Back 36

1. Cyclooxygenase pathway -> PG + TX, 2. lipoxygenase pathway -> leukotrienes + liposins

Front 37

What is the function of Leukotriene C4, D4, E4?

Back 37

Cause broncho constriction (smooth muscle constriction) + vascular smooth muscle constriction (↑ BP)

Front 38

Function of prostaglandin

Back 38

Mediates pain ->promotes vasodilation at sites of inflammation

Front 39

What are the 2 molecules in acute inflammation that mediate pain?

Back 39

1. Bradykinin, 2. prostaglandins

Front 40

If patient has RA -> takes enteric coded aspirin -> what is the side effect?

Back 40

Peptic culcers -> b/c blocking PG that are needed for mucus production in the stomach

Front 41

Put patient on NSAIDS -> pt comes back in few days and is weezing. What is happening?

Back 41

Asprin induced asthma. By blocking cyclooxygenase -> arachidonic acid is building up -> thus its being converted by lipoxygenase -> ↑ [leukotriene] -> induced bronhco constriction

Front 42

What enzyme do steroids inhibit?

Back 42

Steroids (aka glucocorticoids) inhibits PHOSPHOLIPASE A2

Front 43

What enzyme does Aspirin inhibit?

Back 43

cycloxoygenase

Front 44

What is the function of IL-1 + TNF

Back 44

Acute inflammation mediators

Front 45

Platelet activating factor

Back 45

During acute inflammation -> need platelet adhesion -> causes plateletes to stick + generates phospholipase A2(at low concentration it’s a vasodilator + and ↑ concentration it’s a vasoconstrictor)

Front 46

How is platelet factor released?

Back 46

Bee sting-> cytokines produced from toxins of bee -> IL1 + TNF -> mast cell degranulation -> ↑ [histamine] -> release of platelet activating factor

Front 47

What is the function of cytokines and chemokine's

Back 47

Modulate function of other cell types -> mainly from activated lymphocytes and macrophages

Front 48

Which cytokines stimulate hematopoiesis?

Back 48

IL-3 + GM-CSF (granulocyte-monocyte colony stimulating factor)

Front 49

How do you get systemic shock?

Back 49

Bacterial infection -> endotoxin(aka LPS or gram (-)) -> drops in BP

Front 50

Function of chemokine's

Back 50

Stimulate leukocyte recruitment in inflammation and control migration of cells through various tissues

Front 51

What are the acute-phase reactions of IL-1 + TNF?

Back 51

1. Fever, 2. ↑ sleep, 3. ↓ appetite, 4. acute-phase proteins

Front 52

What molecules does NO made from?

Back 52

L-arginine

Front 53

Type I (nNOS)

Back 53

Neuronal nitrogen oxide synthetase- Ca2+ DEPENDENT

Front 54

Type II (iNOS)

Back 54

Inducible - heart - respiratory epithelium -> Ca2+ INDEPENDENT ->induced by IL-1, TNF, IFN-gamma

Front 55

Type III (eNOS)

Back 55

Endothelium - Ca2+ DEPENDENT

Front 56

What are the inflammatory effects of NO?

Back 56

Vasodilation, doesn’t allow platelets to adhere, reduces leukocyte recruitment to the site, antimicrobial effect

Front 57

NO + O2- -> OH- + NO2

Back 57

Function is to kill microbes

Front 58

What are the 3 major types of oxygen free radicals

Back 58

1. Superozide, 2. OH-, 3. HOCl(halide)

Front 59

What happens when ROS gets to high levels

Back 59

Tissue damage -> protease activation -> damages the cell

Front 60

What are the ROS scavengers

Back 60

Catalase -> H2O2 -> H20 + O2, glutathione -> RBC -> scavenge ROS(if no glutathione -> anemic), vitamin E + C (scavenge ROS)

Front 61

What are the molecules that mediate fever?

Back 61

1. IL-1, 2. TNF, 3. Prostaglandins

Front 62

What are the molecules that mediate pain?

Back 62

Prostaglandins and bradykinin

Front 63

What are 3 examples of proteases

Back 63

Elastase, collagenase, cathepsin (in Extracellular matrix)

Front 64

What happens when proteases are released

Back 64

Causes damage by degradation of elastin, collagen, and basement membrane

Front 65

Serous inflammation

Back 65

Blister -> effusion -> outpouring of thin fluid -> edema that is devoid of protein

Front 66

Fibrinous inflammation

Back 66

↑ permeability -> fibrin deposits in extracellular space (fibrinoid exudate); typically involving a mesothelial surface, there is an outpouring of protein rich fluid that results in precipitation of fibrin

Front 67

What are the 2 anti-protease molecules?

Back 67

1. Alpha-2-macroglobin (in serum), 2. alpha-1-antitrypsin (neutrophil)

Front 68

Ulcer

Back 68

Local defect of the surface of an organ or tissue -> produced by sloughing of inflammatory necrotic tissue

Front 69

What bacteria causes peptic ulcer?

Back 69

H. pylori

Front 70

How do we get injury to tissues via inflammation?

Back 70

1. ROS damages the surrounding tissue, 2. leukotriene's -> makes ROS, 3. unchecked ROS

Front 71

How do u protect from wrinkles

Back 71

Use vitamin E cream -> ↓ ROS

Front 72

What is the MOA of Rheumatoid arthritis

Back 72

Wound repair and acute inflammation -> if it doesn't stop -> could be chronic inflammatory response -> ie RA

Front 73

What are some causes of chronic inflammation

Back 73

RA, atherosclerosis, TB, chronic lung disease, alcohol

Front 74

What are the cells that are important in chronic inflammation?

Back 74

1. Macrophages/monocytes, 2. lymphocytes, 3. plasma cells

Front 75

What cell type is damaged in tertiary syphilis

Back 75

Plasma cells

Front 76

What is the cell type that causes damage during chronic inflammation?

Back 76

Macrophages + monocytes

Front 77

What is the process of granulomatous formation in TB?

Back 77

TB -> chronic inflammatory disease -> lungs have holes in apex (cavitations) -> macrophages caused all the holes + giant cells

Front 78

Poly-nuclear macrophages

Back 78

Aka giant cells

Front 79

What is the process of giant cell formation

Back 79

Bee sting -> injected toxins -> stimulates cells to release cytokines -> after a while chemicals/toxins are being handled -> and couldn’t get the bee sting out -> pain via PG + bradykinin -> acute inflammation turns to chronic inflammatory response -> neutorphils keep trying to kill the bee stinger -> macrophages come in to help -> try to phagocytose the bee stinger -> blows up the tissue -> much more destruction -> much more wound repair(fibrosis) -> macrophages are trying to fuse -> turns to "giant cell" inflammation -> they phagocytose foreign object -> lots of tissue damage -> encases the foreign object (granulomatous inflammation) -> now foreign object is no longer in contact w/tissue -> stops inflammation

Front 80

What are the cytokines that initiate giant cell formation?

Back 80

IL-4 + IFN-gamma

Front 81

Viral infections

Back 81

See lymphocytes -> pt comes in and u do a CBC -> see high lvl of lymphocytes -> thus viral infection; if its neutrophils thus it’s a bacterial infection

Front 82

What are the 4 types of granulomatous inflammation

Back 82

1. TB, 2. leprosy, 3. syphilis, 4. cat-scratch disease(bartonella hansale)

Front 83

What is the role of mast cells?

Back 83

Mast cells involved in acute inflammation only

Front 84

What are the soluble mediators from mast cells

Back 84

Histamine, bradykinin

Front 85

What is the MOA of a foreign body granuloma

Back 85

Subcutaneous stitches to bring wounds together (used silk) -> suture is a foreign object -> acute inflammation -> painful -> change over to chronic inflammation -> giant cell inflammation -> form granulomatous -> feels bump

Front 86

What types of cells are seen in granulomatous inflammation

Back 86

Langhans and giant cells

Front 87

Fibrosis

Back 87

Chronic inflammation

Front 88

What is the systemic effect of inflammation

Back 88

Fever -> mediated by hypothalamus or prostaglandin production

Front 89

What does fibrinogin do to RBC?

Back 89

Fibrinogen causes RBC to stack up (ROUleaux) -> causes RBC to sediment (against gravity) -> (+) sedimentation rate -> indicates inflammation

Front 90

What does a (+) SED rate tell us?

Back 90

Indicates inflammation