Path Fall 3 Chronic Inflammation

Front 1

what is the time course for chronic inflammation?

Back 1

prolonged

weeks to months

**beings slow and sort of creeps up on you. insidious onset

Front 2

what 3 processes are happening simoultaneously in chronic imflammation

Back 2

1. inflammation: tissue is infiltrated with MONONUCLEAR cells

2. tissue destruction

3. tissue repair:
-angiogenesis
-fibrosis

Front 3

if we have lots of IL1, TNF and little IL10 for a prolonged period what happens

Back 3

more PRO inflammatory,we get chronic inflammation

Front 4

so acute inflammation can lead to ___ inflammation

Back 4

chronic

**recall the 4 outcomes of acute inflammation were
1. resolution
2. Healing with CT replacement- Fibrosis
3. Abcess formation- pyogenic bugs like staph
4. CHRONIC inflammation

Front 5

how is edema drained

Back 5

via lymphatics

**lymph can also carry protein and the yucky cell bits

Front 6

when will we see lots of monocytes

Back 6

in the later phase (48 hrs) of acute inflammation but macrophages are a hallmark of chronic infection

Front 7

what cells are responsible for clearing necrotic tissue and microbes

Back 7

PMN: acute
Macro: chronic

Front 8

what are some things that can cause chronic inflammation

Back 8

1. persistant infections
2. prolonged exposure to toxic things
3. Autoimmune disease

Front 9

whats our characteristic cell for chronic anflammation? tell me about its course

Back 9

macrophage

*stem cell in bone marrow gives rise to monocyte (blood) and are called macrophages in the tissue. In the tissue they are activated by cytokines or endotoxin

Front 10

whats cool about the whole body and macrophages

Back 10

part of a mononuclear phagocyte system

in different places macro are called different things
-glia: CNA
-Kupfuer: liver
-osteoclast: bone
-alveolar macro: lung

Front 11

macrophages are involved in what 3 things/.

Back 11

1. tissue destruciton
2. vascular proliforation
3. fibrosis

Front 12

we know macr play a role in tissue destruction. do they do anything else?

Back 12

yep. they secrete biologically active things that are also involved in

fibrosis and vasculation proliforation

Front 13

lets tell a story. how does the macro get to the tissue where its neeeded?
how is it activated?
what does it do once in the tissue

Back 13

in chronic inflammation monocytes in teh blood will start to slow and roll, they will then adhere to the BV, and then emigrate out, once in the tissue it migrates to its site of action by chemotaxis. Once its where it needs to be it can be activated by T cells or non immune mediated activation (endotoxin, fibrinectin). The ACTIVE macro can then cause tissue injury or fibrosis (or vascular proliforation). Tissue injury occurs via: ROS, RNS, protease, coagulation, AA metabolism, NO.

Front 14

how can we get large accumulations of macro in chronic inflammation

Back 14

1. the are continualy recruited
2. they locally proliforate (PMN couldnt do this)
3. They are immobilized

Front 15

other than macro what other cells are common in chronic inflammation

Back 15

1. Lymphocytes: B/T, work with macro

2. Plasma Cells: make AB
3. MAST: made histamine, seen in acute also, has receptor for Fc part of IgE
4. Eosinophiles: seen with allergies or parasites. have granules

Front 16

when do we see mast cells?

Back 16

chronic and acute inflammation

**they release histamine
**they also have a receptor for the Fc portion of IgE

Front 17

what is the cell that you like to see bc it can only be a few things?

Back 17

eosinophiles,

can be seen in inflammatory responses due to 1. allergies 2. parasites.
*have granules to destroy stuff

Front 18

why can the presence of T cells and macro potentiate the chronic immune response so well?

Back 18

well a T call can be activated and it then secretes TNF to make MORE inflammation. The T also makes IFNg which activates macro. The activated Macro then secretes more TNF and IL1. The macro also presents Ag to T cells and activates more T cells. The T then does IFNg to recruit MORE macro.

Front 19

so if we see something that looks like chronic inflammation and its been going on for months but we see PMN is it chronic or acute. is there an example of when this is seen

Back 19

its still chronic, PMN may persist for many months in chronic inflammation

**this is seen in osteomyelitis

Front 20

what type of chronic inflammation has a super distinct pattern?

Back 20

Granulomatous Inflammation

**has granulomas, lots of epitheloid like macros, only seen in a few diseases

Front 21

in what disease do we see granulomas?

Back 21

FROM A BUG
1. TB- prbly most common. caseating granuloma (tubercle). langhans giant cell

2. Leprosy- not super common

3. syphalis- also not common

4. Car scratch disease

AUTOIMMUNE:
5. Sarcoidosis: if its none of the others it may be this, disease of elimination

6. Chron's Disease

FUNGI
7. Coccidioidomycosis, valley fever

8. Histoplasmosis

Front 22

what causes... what do they all have in common?

1. TB
2. Leprosy
3. Syphalis
4. Cat Scratch Disease

Back 22

all form granulomas

1. mycobacterium tuberculosis
2. Mycobacterium leprae
3. Treponema pallidum
4. Gram - Bacillus

Front 23

what do granulomas look like

Back 23

epitheloid macrophages with some giant langhan cells surrounded by fibroblasts/leukocytes

**focal area of granulomatous inflammation

Front 24

what is a giant cell, what are the 2 kinds

Back 24

when epetheloid macro fuse

1. Langherhan- nuclei arranged aroudn the periphry

2. Foerign Body- nuclei arranged haphazardly

Front 25

whats the collection of epitheloid macros with their nuclei all arranged peripherally. what would it be if the nuclei were all chaotic

Back 25

giant cells

1. Langerhan: peripheral nuclei
2. Foerign Body: haphazard nuclei

Front 26

how can you tell at micro level if a granuloma is caseating

Back 26

caseating granuloma seen in TB called tubercle

**at micro level the center is amorphous adn has NO nuclei, tihs means they are all dead and necrotic

Front 27

what are the 2 types of granulomas

Back 27

1. Foerign Body: immune component included indigestible parts of prganisms and a T cell mediated immunity to inciting agent

2. Tubercle: caseating granuloma thats seen in TB

Front 28

how can you Dx granulomatous inflammation

Back 28

`1. need a granuloma

look for foerign body, stain to see microorganisms, culture for TB/Fungus, serological studies to ID syphalis. if none of these it must be sarcadoemia

Front 29

what is serous inflammation? where does it come from? when do you see it?

Back 29

its a thin clear fluid

**can be from blood or mesothelial cells. when fluid from mesothelial cells fills a cavity its called effusion

**its the fluid you get with blisters, burns

Front 30

what kind of fluid is in an effusion

Back 30

serous

**mesothelial cells make serous (thin clear watery) fluid and fill a cavity

Front 31

what is teh opposite of a serous inflammation

Back 31

Fibrinous: its thick and sticky, like lots of threads

made of fibrin

Front 32

wwhat is fibrinous inflammation

Back 32

its a thick exudate that is stringy.

made of fibrin

Front 33

where are a few places we saw fibrinious exudate

Back 33

apendicitis and pericarditis

Front 34

with a fibrinous exudate what are the 2 outcomes

Back 34

1. Resolution due to fibrinolysis

2. Organization of fibers into a scar, fibrin is NOT removed

Front 35

what happens if fibrin from a fibrinous exudate is not cleared by fibrinolysis

Back 35

its organized into a scar

**it restricts movement and needs to be removed. think pericarditis, teh heart now rubs the sac

Front 36

what is purulent inflammation

Back 36

pus- PMN, necrotic cells, edema

**made from pyogenic bugs like staph

Front 37

what bug might make a suppurative inflammation

Back 37

purulent**

**staphylococci

Front 38

what is an abcess

Back 38

a local collection of purulent material rimmed with PMN and repaired tissue

**its a walled off infection, it can be superficial or deep in tissue. AB cant get to it so it needs to be drained

Front 39

what is a local defect in an organ thats caused by shedding of inflammatory necrotic tissue?

what is a localized region of necrotic tissue walled off with an outer region of repair?

Back 39

ulcer

abcess

Front 40

where are ulcers most common

Back 40

1. GI- mouth, stomach, intestine

2. LE of older folks, decreased blood flow

Front 41

what does fibrin exudate look like at micro

Back 41

lots of thin pink strings

Front 42

what is a crater in the tissue that used to be full of necrotic tissue

Back 42

ulcer

Front 43

how is edematous fluid filtered/taken away

Back 43

lymphatics

**lymphatics contain edema fluid, leukocytes, and cellular debris

Front 44

what kinds of things are found in lymph?

Back 44

cell debris
leukocytes
edematous fluid

Front 45

what is lymphangitis?
what is lymphadentitis?

Back 45

2nd inflammed lymphatics

drainging LN that are inflammed, nodes show hyperplasia of lymphoid follicles and sinusoidal cells

Front 46

what is it called when lymphatics are secondarily inflammed?

Back 46

lymphangitis

*lymohadenitis is when drianing LN are inflammed. Nodes show hyperplasia of lymphoid follicles and sinusoidal cells.

Front 47

what mediates the systemic effects of inflammation

Back 47

TNF
IL1
IL6

*fever, increased WBC, increased acutephase protein, sepsis

Front 48

what are the 4 systemic indicators of infection

Back 48

IL1 IL6 TNF mediated

**fever
**increased WBC- leukocytosis
**increased acute phase protein
**sepsis

Front 49

why do you get a fever with infection

Back 49

IL1, TNF IL6 PG

**fever is a response to pyrogen

Front 50

what is a pyrogen

Back 50

its a bug that causes a fever

Front 51

why do NSAIDS reduce fever

Back 51

they inhibit COX so no PG are made, no PG means no fever

Front 52

do PG cause fever

Back 52

yep, this is why we take NSAIDS to decrease fever. we block COX so no PG are made

TNF, IL1 IL6 and PG ALL lead to fever

Front 53

what are acute phase proteins

Back 53

CRP (c reactive protein)
Fibrinogen
serum amyloid A (SAA)

**these are proteins made by the liver that are expressed at normal levels but super high levels with systemic effects of inflammation
**syntheiss is upregulated by cytokines

Front 54

if we have increased fibrinogem serum amyloid a protein adn CRP what do we think?

Back 54

systemic effects of INFLAMMATION

**increased plasma levels of acute phase proteins

Front 55

what is leukocytosis

Back 55

general term for increased WBC count as seen as a systemic response of inflammation

Front 56

what is granulomatous inflammation?

Back 56

its type of CHRONIC inflammation that is characterized by granulomas

**dif than granulomatous tissue which is fibroblasts and BV that are involved in tissue repair

Front 57

what diseases are ddx ffor granulomatous inflammation

Back 57

1. TB- caseating granuloma
2. Leporacy
3. Syphalis- Cat scratch
4. Sarcoidosis
5. Chrons
6. Cocci (valley fever)

Front 58

so in TB you see what type of granuloma

Back 58

caseating, cheese like

Front 59

if you see a granuloma whats the DDx

Back 59

1. TB
2. Cocci
3. Cat scratch
4. Chrons
5. Leprocy
6. Syphalis

Front 60

what are the 2 main parts of a granuloma

Back 60

1. Epitheloid macrophage

2. Giant cells

3. Ribbed by fibroblasts and CT

Front 61

what are the 2 types of giant cells? what are the 2 types of granulomas?

Back 61

Giant:
1. Langerhan: peripheral nuclei
2. Foerign Body: haphazard nuclei

Granuloma:
1. Immune:
2. Foreign Body

Front 62

what is the prototype of an immune granuloma caused by? how is it distungiushed from other granulomas

Back 62

TB

**TB is caseating, it looksl ike cheese and has its own wpecial name called a tubercle

Front 63

what is a 2nd inflammation of the lymphatics calld

Back 63

lymphangitis

Front 64

what is it called when draining LN are inflammed

Back 64

lymphadenitis

**nodes show hyperplasia of lymph follicles and sinusoidal cells

Front 65

what is lymphangitis and lymphadenitis

Back 65

lymphangitis is 2nd inflammation

lymphadenitis is when draining LN are inflammed and there may be hyperplasia of lymphoid follicles

Front 66

what is leukocutosis

Back 66

increased WBC, general term

Neutrophilia- increased PMN, due to bacteria

Lymphocytosis- due to virus

Eosinophilia- parasites, asthma, hay fever

Front 67

what cell is elevated in bacterial infection? what cell is elevatedin viral infection? what about parasites?>

Back 67

Bacteria- PMN

Virus- Lymphocytes

Parasite- eosionophile

Front 68

what is lymphopenis

Back 68

decreased WBC

can be due to things like typhoid fever or in ppl who cant mount an immune response

Front 69

so we know that we have increased acute phase proteins in systemic infections, what are some of these clinical manifestations

Back 69

icnreased HR
increased BP
Rigors
Chills
Anorexia
Somnolence
Malaise

Front 70

what is cachexia associated with

Back 70

wasting syndrome associated with acute phase response (systemic infection)

**chronic inflammation

Front 71

what is sepsis caused by? what factors are released

Back 71

caused by lots of LPS (gram neg) in the blood

lots of TNF nad IL1 are released, this can cause DIC, hypoglycemia, hypotensive shock

Front 72

what is a disease caused by defective inflammation? waht about excessive inflammation

Back 72

GCD, decreased oxidative burst, not enough ROS to kill the bug

Excess seen in allergies, autoimmune disorders, etc

Front 73

Leukocytosis
shift to left
neutrophilia
pmyphocytosis
eosionophilia
Leucopenia
Lymphopenia

Back 73

Leukocytosis: increased WBC
Shift to Left: increase in immature PMN, called band cells
Neutrophilia: increased PMN, seen with bacterial infection
Lymphocytosis: increased lymphocytes, seen in viral
Eosinophilia: seen with parasitic infection, asthma, hay fever
Leucopenia: decreased WBC
Lymphopenia; Decreased wbc