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Flashcards in Inflammation Deck (35):
1

Apoptosis

ATP-dependent programmed cell death.

Intrinsic and extrinsic pathways; both pathways activate ____ (cytosolic proteases) > cellular
breakdown including cell shrinkage, chromatin condensation, membrane blebbing, and formation of apoptotic bodies, which are then phagocytosed.

Characterized by deeply ____ cytoplasm and ____ nucleus, ____ (nuclear
shrinkage), and ____ (fragmentation caused by endonuclease-mediated cleavage).

Cell membrane typically remains ____ without signi cant inflammation (unlike necrosis).

DNA laddering (fragments in multiples of ____ bp) is a sensitive indicator of apoptosis.

caspases
eosinophilic
basophilic
pyknosis
karyorrhexis

intact
180

2

Intrinsic (mitochondrial) pathway

Involved in tissue remodeling in embryogenesis. Occurs when a regulating factor is withdrawn from a proliferating cell population (eg, decreased ____ after a completed immunologic reaction > apoptosis of proliferating effector cells).
Also occurs after exposure to injurious stimuli (eg, radiation, toxins, hypoxia).

Regulated by ____ family of proteins. BAX and BAK are ____, while Bcl-2 and Bcl-x are ____.

Bcl-2 keeps the mitochondrial outer membrane impermeable and therefore prevents ____ release from the inner mitochondrial matrix. Bcl-2 overexpression (eg, ____) > decreased caspase activation > tumorigenesis.

IL2
Bcl-2
propapototic
antiapoptotic

cytochrome c
follicular lymphoma t[14;18]

3

Extrinsic (death receptor) pathway

2 pathways:
____ interactions (FasL binding to Fas [CD95] or TNF-α binding to its receptor)
____ (cytotoxic T-cell release of perforin and granzyme B)

____ interaction is necessary in thymic medullary negative selection. Mutations in Fas increase numbers of circulating ____ due to failure of clonal deletion.
Defective Fas-FasL interactions cause ____.

ligand receptor
immune cell

Fas-FasL
self-reacting lymphocytes
autoimmune lymphoproliferative syndrome

4

Necrosis

Enzymatic degradation and protein denaturation of cell due to exogenous injury > intracellular components leak. ____ process (unlike apoptosis).

inflammatory

5

Coagulative necrosis

Seen in
Ischemia/infarcts in most tissues (except ____)

Due to
____ or infarction; proteins denature, then ____ degradation

Histology
Cell outlines ____ but ____ disappear; cytoplasmic binding of ____ dye

brain
ischemia
enzymatic
preserved
nuclei
eosin

6

Liquefactive necrosis

Seen in
____, brain infarcts

Due to
____ release lysosomal enzymes that digest the tissue; ____ degradation firrst, then proteins denature

Histology
Early: cellular debris and ____
Late: cystic spaces and ____ (brain)
____ and cell debris seen with bacterial infection

bacterial abscesses
neutrophils
enzymatic
macrophages
cavitation
neutrophils

7

Caseous necrosis

Seen in
____, systemic fungi
(eg, ____), Nocardia

Due to
____ wall off the infecting microorganism granular debris

Histology
Fragmented cells and debris surrounded by ____ and macrophages

TB
histoplasma capsulatum
macrophages
lymphocytes

8

Fat necrosis

Seen in:
Enzymatic: acute ____ (saponification of peripancreatic fat)
Nonenzymatic: ____ (eg, injury to breast tissue)

Due to:
Damaged cells release ____ to break down triglycerides, liberating fatty acids to bind ____ > saponification

Histology:
Outlines of dead fat cells without peripheral ____; saponification of fat (combined with Ca2+) appears ____ on H&E stain

pancreatitis
traumatic

lipase
Ca++

nuclei
dark blue

9

Fibrinoid necrosis

Seen in
Immune reactions in ____ (eg, polyarteritis nodosa), ____, malignant hypertension

Due to
____combine with fibrin > vessel wall damage (____ reaction)

Histology
Vessel walls are thick and ____

vessels
preeclampsia
immune complexes
type III hypersensitivity
pink

10

Gangrenous necrosis

Seen in
Distal extremity and ____, after ____ ischemia

Due to
Dry: ____
Wet: ____

Histology
Dry: ____
Wet: ____ superimposed on coagulative

GI tract
chronic

ischemia
superinfection

coagulative
liquefactive

11

Leukocyte extravasation

1. Margination and rolling— defective in leukocyte adhesion deficiency ____ ( decreased ____)

Vasculature/stroma:
____ (upregulated by TNF and IL-1)
____ (released from Weibel-Palade bodies)
____, CD34

Leukocyte:
____
____
____

type 2
sialyl-lewisX

e-selectin
p-selectin
GlyCAM1

sialyl-lewisX
sialyl-lewisX
L-selectin

12

Leukocyte extravasation

2. Tight binding (adhesion)— defective in leukocyte adhesion de ciency ___ (decreased ___)

Vasculature/stroma:
___ (CD54)
___ (CD106)

Leukocyte:
___ integrins (LFA-1, Mac-1)
___ integrin

type I
CD18 integrin subunit
ICAM-1
VCAM-1

CD11/18
VLA-4

13

Leukocyte extravasation

3. ___—WBC travels between endothelial cells and exits blood vessel

Vasculature/stroma:
____ (CD31)

Leukocyte:
___ (CD31)

diapedesis
PECAM-1
PECAM-1

14

Leukocyte extravasation

4. Migration—WBC travels through interstitium to site of injury or infection guided by chemotactic signals

Vasculature/stroma:
Chemotactic products released in response to bacteria: ____, IL-8, ____, kallikrein, ____

Leukocyte:
Various

C5a
LTB
platelet-activating factor

15

Free radical injury

Free radicals damage cells via membrane lipid peroxidation, protein modification, and DNA breakage.

Initiated via ____ exposure (eg, cancer therapy), metabolism of drugs (____), redox reactions, ____ (eg, inflammation), transition metals, WBC (eg, neutrophils, macrophages) oxidative burst.

Free radicals can be eliminated by scavenging enzymes (eg, ____, superoxide dismutase, ____), spontaneous decay, antioxidants (eg, ____, C, E), and certain metal carrier proteins (eg, ____, ceruloplasmin).

Examples:
Oxygen toxicity: ____ of prematurity (abnormal vascularization), bronchopulmonary
dysplasia, ____ injury after thrombolytic therapy

Drug/chemical toxicity: ____ and acetaminophen overdose (hepatotoxicity)

Metal storage diseases: ____ (iron) and ____ disease (copper)

radiation
phase I
nitric oxide

catalase
glutothione peroxidase

vitamin A
transferrin

retinopathy
reperfusion

carbon tetrachloride
hemochromatosis
wilson

16

Scar formation
70–80% of tensile strength regained at ____ months; ____ additional tensile strength will be regained afterward.

3
minimal

17

Scar formation

Hypertrophic

Collagen synthesis: ____
Collagen organization: ____
Extent of scar: ____
Recurrence: ____
Predisposition: ____

increased (type III collagen)
parallel
confined to borders of original wound
infrequent
none

18

Scar formation

Keloid
Collagen synthesis: ____
Collagen organization: ____
Extent of scar: ____
Recurrence: ____
Predisposition: ____

INCREASED ALOT (disorganized I and III collagen)
disorganized
extends BEYOND borders of wound with "claw-like" projections on earlobes, face, upper extremeties
frequent
increased incidence in darker skin ethnic groups

19

Tissue mediators

PDGF
Secreted by activated ____ and ____
Induces vascular remodeling and ____ cell migration
Stimulates ____ growth for collagen synthesis

FGF
Stimulates ____

EGF
Stimulates cell growth via ____ kinases (eg,
EGFR/ErbB1)

TGFb
____, fibrosis

Metalloproteins
____

VEGF
Stimulates ____

platelets
macrophages
smooth muscle
fibroblast

angiogenesis

tyrosine

angiogenesis
tissue remodeling
angiogenesis

20

Phase of wound healing:
Inflammatory (up to 3 days after wound)

Effector cells: ____, neutrophils, ____

Characteristics: Clot formation, increased ____ permeability and neutrophil migration into tissue; macrophages clear debris ____ days later

platelets
macrophages
vessel
2

21

Phase of wound healing:
Proliferative (day 3-weeks after wound)

Effector cells: Fibroblasts, ____, endothelial cells, ____, macrophages

Characteristics: Deposition of granulation tissue and ____ collagen, angiogenesis, epithelial cell proliferation, ____ of clot, and wound contraction (mediated by ____)
Delayed wound healing in ____ deficiency and copper deficiency

myofibroblasts
keratinocytes

type III
dissolution
myofibroblasts
vitamin C

22

Phase of wound healing:
Remodeling (1 week-6+ months after wound)

Effector cells: ____

Characteristics:
Type III collagen replaced ____ collagen, increased ____ of tissue
Delayed wound healing in ____ deficiency

fibroblasts
type I
tensile strength
zinc

23

Granulomatous diseases

Bacterial:
Mycobacteria (____, leprosy)
Bartonella henselae (____ disease)
Listeria monocytogenes (____)
Treponema pallidum (____)

Fungal: endemic mycoses (eg, ____)

Parasitic: ____

Chronic granulomatous disease
Autoinflammatory:
Sarcoidosis
Crohn disease
Primary biliary cirrhosis
Subacute (de Quervain/granulomatous)
thyroiditis
Granulomatosis with polyangiitis (Wegener)
Eosinophilic granulomatosis with
polyangiitis (Churg-Strauss)
Giant cell (temporal) arteritis
Takayasu arteritis

Foreign material: ____, talcosis, hypersensitivity pneumonitis

tuberculosis
cat scratch
granulomatosis infantiseptica
tertiary syphilis

histoplasmosis

schitosomiasis

berylliosis

24

Granulomatous diseases

Granulomas are composed of epithelioid cells (____ with abundant pink cytoplasm) with surrounding multinucleated giant cells and ____.

Th1 cells secrete ____, activating macrophages. ____ from macrophages induces and maintains granuloma formation.

____ drugs can, as a side effect, cause sequestering granulomas to break down, leading to disseminated disease. Always test for ____ before starting anti- TNF therapy.

Associated with hypercalcemia due to ____ production.

____ necrosis is more common with an infectious etiology (eg, TB). Diagnosis of sarcoidosis requires ____ granulomas on biopsy.

macrophages
lymphocytes

IFN-gamma
TNF-alpha

Anti-TNF
latent TB

calcitriol (1,25-[OH]2 vitamin D3)

caseating
noncaseating

25

Exudate

____ (cloudy)
____ protein (> 2.9 g/dL)
____ LDH (vs serum)

Due to:
____ (chylous)
Inflammation/infection
____

cellular
increased
increased
lymphatic obstruction
malignancy

26

Transudate

____ (clear)
____ protein (< 2.5 g/dL)
____ LDH (vs serum)

Due to:
increased ____ pressure (eg, HF, Na+ retention)
decreased ____ pressure (eg, cirrhosis, nephrotic)

hypocellular
decreased
decreased

hydrostatic
oncotic

27

Light criteria

Diagnostic analysis comparing serum and pleural fluid protein and LDH levels.

Pleural effusion is exudative if ≥ 1 of the following criteria is met:
Pleural effusion protein/serum protein ratio > ____
Pleural effusion LDH/serum LDH ratio > ____
Pleural effusion LDH > ____ of the upper limit of normal for serum LDH

0.5
0.6
2/3

28

Erythrocyte sedimentation rate

Products of inflammation (eg, fibrinogen) coat RBCs and cause aggregation. The ____ RBC aggregates fall at a faster rate within a pipette tube. Often co-tested with ____ levels.


denser
CRP

29

Increased ESR:
Most ____
Infections
____ (eg, giant cell [temporal] arteritis,
polymyalgia rheumatica)
Cancer (eg, metastases, multiple myeloma)
____ (end-stage or nephrotic syndrome) Pregnancy

Decreased ESR:
____ (altered shape) Polycythemia (increased ____ “dilute” aggregation
factors)
____
Microcytosis
____

anemias
inflammation
renal disease

sickle cell anemia
polycythemia
microcytosis
hypofibrinogenemia

30

Amyoidosis

Abnormal aggregation of proteins (or their fragments) into ____ linear sheets > insoluble fibrils > cellular damage and apoptosis.

Amyloid deposits visualized by ____, polarized light (apple green birefringence), and ____ (shows deposits in glomerular mesangial areas [white arrows], tubular basement membranes [black arrows]).

beta-pleated
congo red stain
H&E

31

Amyloidosis

AL (primary)

Due to deposition of proteins from ____. Can occur as a plasma cell disorder or associated with ____. Often affects multiple organ systems, including ____ (nephrotic syndrome), cardiac (restrictive cardiomyopathy, arrhythmia), ____ (easy bruising, splenomegaly), GI (hepatomegaly), and ____ (neuropathy).

Ig light chains
multiple myeloma
renal
cardiac
neurologic

32

Amyloidosis

AA (secondary)

Seen with chronic inflammatory conditions such as ____, IBD, ____, familial Mediterranean fever, protracted infection.

Fibrils composed of ____. Often multisystem like ____ amyloidosis.

rheumatoid arthritis
spondyloarthropathy
serum amyloid A
AL

33

Amyloidosis

Dialysis-related
Fibrils composed of ____ in patients with ESRD and/or on long-term dialysis. May present as ____.

Heritable
Heterogeneous group of disorders, including familial amyloid polyneuropathies due to ____ gene mutation

Age-related (senile) systemic
Due to deposition of normal (wild-type) transthyretin (TTR) predominantly in ____. ____ progression of cardiac dysfunction relative to AL amyloidosis.

B2-microglobulin
carpal tunnel syndrome

transthyretin

cardiac ventricles
slower

34

Amyloidosis

Organ-specific
Amyloid deposition localized to a single organ.

Most important form is amyloidosis in Alzheimer disease due to deposition of β-amyloid protein cleaved from ____.

Islet amyloid polypeptide (IAPP) is commonly seen in ____ and is caused by deposition of amylin in pancreatic islets.

Isolated atrial amyloidosis due to ____ is common in normal aging and can
predispose to increased risk of ____.

Amyloid deposition to ventricular endomyocardium in ____.

____ deposition in tumor cells in medullary carcinoma of the thyroid.

amyloid precursor protein (APP)

diabetes mellitus type 2

natriruetic peptide

restrictive cardiomyopathy

calcitonin

35

Lipofuscin
A ____ “wear and tear” pigment associated with normal ____.

Formed by oxidation and polymerization of autophagocytosed ____.

Autopsy of elderly person will reveal deposits in heart, colon, liver, kidney, eye, and other organs.

yellow-brown
aging

organellar membranes