Inflammation

Question 1

DNA laddering

Answer 1

During karyorrhexis, endonucleases cleave DNA into fragments in multiples of 180bp - indicator of apoptosis

Question 2

Intrinsic pathway of apoptosis

Answer 2

Changes in proportion of anti- and pro-apoptotic factors –> increased mt perm and cyt c release

When regulating factor is withdrawn from proliferating cell pop or after exposure to injurious tim

Question 3

Proapop proteins

Answer 3

BAX, BAK

Question 4

Anti-apop

Answer 4

Bcl2 (binds and inhibits Apaf-1, so don’t activate caspases)

Bcl2 overexp implicated in cancers

Question 5

Extrinsic pathway of apoptosis

Answer 5

FasL binds Fas (CD95) - eg thymic medullary negative selection to get rid of self-reactive lymphocytes –> Fas mcs get together and bind FADD –> binds and activates caspases

Immune cell (eg CD8) releases perforin and granzyme –> activates caspases inside cell

Question 6

Types of necrosis

Answer 6

Coagulative - ischemia/infarcts (proteins denature, then enzymes degrade)

Liquefactive - bacterial abscess, brain infarcts -PMNs release enzymes that degrade, then proteins denature

Caseous - TB, systemic fungi, macrophages wall off

Fat - acute pancreatitis (lipases = released), breast trauma

Fibrinoid - immune rxn in vessels (IC deposit with fibrin and damage walls)

Gangrenous - distal extremity from chronic ischemia (dry) +/- superinfxn (wet)

Question 7

Acute vs. chronic inflammation - cells/mcs that mediate and outcomes

Answer 7

Acute - neutrophil, eos, antibodies; can –> resolution, abscess formation, or progression to chronic inflamm

Chronic - mononuclear cells + fibroblasts –> blood vessel prolif and fibrosis

Question 8

Chromatolysis

Answer 8

Axon injury in neuron –> increased protein synth to try to repair –> round cellular swelling with displaced nucleus, dispersion of nissl substance throughout cytoplasm

Question 9

Dystrophic calcification

Answer 9

Localized deposition of ca in abnormal tissues, usually normocalcemic

eg TB, liquefactive necrosis of chronic abscesses, fat necrosis, thrombi, toxo etc

Question 10

Metastatic calcification

Answer 10

widespread deposition of Ca in normal tissue, secondary to hypercalcemia or high calcium-phosphate product levels (eg chronic renal failure with 2ary hyperparathyroidism)

Mostly in kidney, lung, and GI mucosa (all lose acid quickly and increased pH favors deposition)

Question 11

Margination and rolling receptors

Answer 11

E/P-selection (on epith) - Sialyl-Lewis (on PMN)

GlyCAM1,CD34 (endoth) - L-selectin (PMN)

Question 12

Leukocyte binding to endothelium - receptors

Answer 12

ICAM (CD54) and VCAM (CD106) on endothelium bind CD11/18 and VLA4 on leukocyte

Question 13

Diapedesis - receptors

Answer 13

PECAM-1 (CD31)

Question 14

Tissue mediators of wound healing that stimulate angiogenesis

Answer 14

FGF
TGF-beta
VEGF

Question 15

PDGF

Answer 15

Tissue mediator secreted by activated plts and macrophages –> vascular remodeling and smooth m. migration

Stimulates fibroblasts –> coll deposn

Question 16

EGF

Answer 16

Stimulates cell growth via tyrosine kinases

Question 17

Metalloproteinases

Answer 17

Tissue remodeling

Question 18

Three phases of wound healing

Answer 18

1. Inflamm (0-3d)
2. Proliferative (3d-weeks) - granulation tissue, wound contraction, dissolve clot
3. Remodeling (1 week-6+ months) - fibroblasts replace Type III coll with Type I coll to increase tensile strength

Question 19

Granuloma formation

Answer 19

Th1 –> IFN-gamma –> activate macrophages, which secrete TNF-alpha that induces and maintains granulomas; anti-TNF drugs break granulomas up, can –> dissem dz

Question 20

Bugs that –> granulomatous dz

Answer 20

Bartonella
Francisella
Listeria
Mycobacterium (leprae and tb)
Treponema pallidum
Schistosomiasis

Also sarcoidosis and Crohn dz (noncaseating

Question 21

Exudate vs. transudate

Answer 21

Exudate = thick, protein-rich

Transudate = thin, hypocellular

Question 22

Amyloidosis - types

Answer 22

AL (primary): deposition of proteins from Ig light chains; Plasma cell disorder or associated with multiple myeloma; Often affects multiple organ systems

AA (secondary) - chronic inflamm, serum Amyloid A, multisystem

Dialysis-related (beta2-microglobulin, may present as carpal tunnel)

Heritable - heterogeneous

Age-related systemic (normal transthyretin deposited, eg in myocardium)

Organ-specific (eg AD, IAPP in DM2)

Question 23

Lipofuscin

Answer 23

“Wear and tear” pigment - see it with age from autophag of organellar membranes

Question 24

Karyorrhexis

Answer 24

Nuclear fragmentation