Acute and Chronic Inflammation

Question 1

What are the two functions of inflammation?

Answer 1

Destroy/contain the harmful agent and prepare for the occurence of healing/repair

Question 2

What are the four cardinal signs of inflammation?

Answer 2

Heat, redness, swelling, pain (and loss of function)

Question 3

What are the features of acute inflammation?

Answer 3

• fast onset (min-hr)
• mainly neutrophil infiltrate
• usually mild/self-limiting tissue injury
• prominent local and systemic signs

Question 4

What are the features of chronic inflammation?

Answer 4

• slow onset (days)
• monocyte/macrophage and lymphocyte infiltrate
• often severe/progressive tissue injury
• less prominent local and systemic signs

**chronic inflammation may follow acute or arise de novo

Question 5

What are the common causes of inflammation?

Answer 5

• Infections/microbial toxins (bacteria, viruses, fungi, parasites)
• Tissue necrosis (ischemia, trauma, etc)
• Foreign bodies (splinters, sutures, etc)
• Immune/hypersensitvity reactions
  
  • environmental substances
  • self antigens

Question 6

What 3 ways are abnormal stimuli recognized by the body?

Answer 6

1. Cells with receptors to detect infectious pathogens (epithelial, DCs, phagocytes, TLRs)
2. Cell receptors that recognize molecular structures present with cell damage (e.g. inflammasomes recognize parts of dead cells in cytoplasm such as uric acid/DNA/ATP and activate caspase-1/IL-1 to recruit leukocytes)
3. Circulating proteins (i.e. complement)

Question 7

What are the three components of acute inflammation?

Answer 7

1. Small vessel dilation (induced by histamine and nitric oxide… affects arterioles then capillary beds)
2. Increased permeability of small vessels (induced by histamine and bradykinin… affects mainly venules)
3. Margination/emigration of leukocytes from circulation, leukocyte activation

Question 8

What causes the erythema and warmth associated with inflammation?

Answer 8

Stasis of blood flow/congestion due to the vasodilation of small vessels

**Think wider river= slow flowing, fast little stream

Question 9

Define exudate

Answer 9

Inflammatory extravascular fluid with high protein content that may contain some white and red cells

*High specific gravity >1.020

**More serious inflammation process than the leakage of transudate, caused by alteration in normal vessel permeability

Question 10

Define transudate

Answer 10

Non-inflammatory extravascular fluid with low protein content and few cells (ultrafiltrate of plasma)

*Low specific gravity <1.012

**Leakage due to increased hydrostatic pressure/decreased colloid osmotic pressure… more mild than exudate leakage

Question 11

Define pus

Answer 11

Purulent thick exudate rich in leukocytes

Question 12

Define edema

Answer 12

Excess fluid in interstitium or serosal cavities

Question 13

Describe how histamine is released and its effect on vessels

Answer 13

• Released from mast cells in connective tissue in response to cytokines (IL1), trauma, complement, etc
• Causes vasodilation and increased vascular permeability

Question 14

Describe how nitric oxide is released and its effect on vessels

Answer 14

• Many functions/origins
• In inflammation; released by endothelial cells in response to injury and causes vasodilation

Question 15

Describe what bradykinin is and its effect on vessels

Answer 15

• Plasma protein resulting from kinin system activation (exposure to site of endothelial injury)
• Causes vasodilation, increased permeability, and pain

Question 16

What is the origin of neutrophils? macrophages?

Answer 16

Neutrophils are from hematopoietic stem cells in marrow

Macrophages are from hematopoietic stem cells in marrow in inflammatory reactions AND many tissue-resident macrophages come from stem cells in development

Question 17

What is the life span of neutrophils? macrophages?

Answer 17

Neutrophils= 1-2 days (short)

Inflammatory Macrophages= days-weeks (long)

Tissue-resident Macrophages= years (long)

Question 18

What is the response of neutrophils to stimuli? of macrophages?

Answer 18

Neutrophils= rapid, short-lived response

Macrophages= more prolonged, slower, dependent on new gene transcription

Question 19

Define leukocyte margination

Answer 19

Movement closer to vessel wall (due to vasodilation and stasis)

Question 20

What are the two main adhesion molecules that help with rolling/adhesion of leukocytes to the endothelial cells?

Answer 20

Selectins (on endothelial cells, platelets, leukocytes); not present until cell activation by mediators (histamine, thrombin, etc)… aid in rolling and loose attachment

Integrins (on leukocytes) activated by chemokines on endothelial cells… results in stable attachment

Question 21

Define diapedesis

Answer 21

Movement of leukocytes through vessel walls (cells squeeze through endothelial cells, driven by chemokine CD31/PECAM1 on leukocytes and endothelial cells)

Question 22

Define chemotaxis

Answer 22

Movement along a chemical gradient (after crossing vessel wall, cells migrate towards injury site via gradients of chemokines/complement/leukotrienes)

Question 23

What are the results of leukocyte activation?

Answer 23

1. phagocytosis
2. intracellular destruction
3. release of substances that destroy dead tissue and microbes
4. more mediator production (amplify inflammatory reaction)

Question 24

What substances act to activate leukocytes?

Answer 24

Microbes, necrotic tissue, mediators (activate leukocytes after recruitment to the site of injury)

Question 25

What two ways can leukocytes recognize a microbe?

Answer 25

1. Specific surface receptors for microbe on the leukocyte 2. Receptors for opsonins (IgG, complement, lectins)

Question 26

What two mediators induce vasodilation? Where do they come from?

Answer 26

1. Histamine (from mast cells, basophils, platelets) 2. Nitric oxide (from endothelium and macrophages)

Question 27

What two mediators increase vascular permeablity? Where do they come from?

Answer 27

1. Histamine (from mast cells, basophils, platelets) 2. Bradykinin (from plasma; produced in liver)

Question 28

What two mediators induce chemotaxis/recruitment/activation of leukocytes? Where do they come from?

Answer 28

1. IL1/TNF (from macrophages, endothelial cells and mast cells) 2. Bacterial products (from bacteria lol duh)

Question 29

What two mediators induce fever? Where do they come from?

Answer 29

IL1/TNF (both from macrophages, endothelial cells, and mast cells)

Question 30

What mediator induces pain? Where does it come from?

Answer 30

Bradykinin from mast cells, leukocyted, and plasma (produced in the liver)

Question 31

What two mediators induce tissue damage? Where do they come from?

Answer 31

1. ROS (from leukocytes) 2. Nitric oxide (from endothelium and macrophages)

Question 32

What are some common defects in leukocyte inflammation function?

Answer 32

1. Production defect (BM suppression from chemo/radiation) 2. Adhesion/chemotaxis defect (spesis, diabetes, dialysis, malignancy) 3. Phagocytosis and microbicidal activity defect (sepsis, diabetes, anemia, malnutrition) \*\*Genetic defects are RARE

Question 33

What are the general characteristics of all acute inflammation?

Answer 33

1. Accumulation of leukocytes (**neutrophils** and macrophages) \*\*NOT lymphocytes! 2. Fluid build up in extracellular tissue 3. Dilation of small blood vessels

Question 34

What are the subtypes of acute inflammation?

Answer 34

1. _Serous_ 2. _Fibrinous_ 3. _Suppurative/purulent_

Question 35

Describe serous inflammation

Answer 35

Most mild type of acute inflammation; outpouring of transudate E.g. Effusions or blisters

Question 36

Describe fibrinous inflammation

Answer 36

"in between" acute inflammation severity, fibrinogen leakage converts to fibrin -\> scarring \*\*Affects linings (meninges, pericardium, pleura, etc) E.g. Pericarditis, pleuritis, peritonitis

Question 37

Describe suppurative inflammation

Answer 37

Most severe acute inflammation, **large # of neutrophils** with necrotic cells, edema fluid and bacteria -\> PUS \*\*More likely with pyogenic (e.g. staph) bacteria E.g. Acute appendicitis, bronchopneumonia, meningitis

Question 38

Define ulcer

Answer 38

Local defect on the surface of an organ/tissue characterized by sloughing of surface and necrotic inflammatory tissue E.g. peptic ulcer, skin ulcer (esp with diabetes)

Question 39

Define chronic inflammation

Answer 39

Active inflammation, tissue injury, and healing occuring at the same time for **months to years**

Question 40

What are the common causes of chronic inflammation?

Answer 40

1. Persistent infections (e.g. TB, syphilis, chronic lung abscess) 2. Prolonged exposure to toxic agents (exogenous e.g. silicosis, or endogenous e.g. atherosclerosis) 3. Hypersensitivity diseases (autoimmune or allergy)

Question 41

What characterizes chronic inflammation?

Answer 41

1. Infiltration by mononuclear cells (macrophages, lymphocytes, plasma cells) 2. Tissue destruction (by persistent injurious agent and/or inflammatory cells) 3. Attempts at healing (angiogenesis and fibrosis)

Question 42

What are the two types of granuloma?

Answer 42

1. _Immune_ (from persisten microbe or self-antigen) E.g. TB, syphilis, Crohn's, autoimmune 2. _Foreign body_ (from inert foreign bodies without a T cell mediated immune response) E.g. sutures, splinters

Question 43

Describe granulomatous inflammation

Answer 43

* Aggregates of epithelioid histiocytes (macrophages) * _Multinucleated giant cells_= fusion of many **macrophages** (induced by IFN gamma) * Collar of **lymphocytes/plasma cells** with surrounding fibrosis \*\*Seen in TB and with foreign bodies/other infections

Question 44

What are the systemic effects of inflammation?

Answer 44

Called "acute phase response": * reaction to cytokines (TNF, IL1, IL6) * fever * elevated plasma levels of acute-phase proteins * leukocytosis

Question 45

What causes fever in the inflammatory response?

Answer 45

_Pyrogens_ (exogenous such as bacterial endotoxins or endogenous such as IL1/TNF from leukocytes) \*\*Pyrogens cause production of **PGE₂** (which stimulates hypothalamus to reset at a higher temp)

Question 46

What are some examples of acute-phase proteins? What are their actions?

Answer 46

\*\*synthesized in liver, **stimulated by IL6;** 1. C-reactive protein (CRP) 2. Fibrinogen 3. Serum amyloid A protein (SAA) \*\*Actions: * bind microbe wall (aid in elimination) * **fibrinogen** binds erythrocytes, causing stacks (rouleaux) that sediment more rapidly than normal resulting in: * elevation of erythrocyte sedimentation rate (ESR) * increased **sed rate** in ingections/autoimmune inflammatory disorders

Question 47

What stimulates leukocytosis? What is the WBC count that defines leukocytosis?

Answer 47

Stimulated by TNF and IL1 WBC count usually high (between 15,000-20,000 cells/mL) because of accelerated release of cells from BM

Question 48

What are the four main types of leukocytosis and what underlying cause do they reflect?

Answer 48

1. Neutrophilia- bacterial infection ("left shift"/accelerate release of immature neutrophils) 2. Lymphocytosis- viral infection 3. Eosinophilia- allergies, asthma, parasitic infection 4. Leukopenia- typhoid, rickettsiae, some protozoans