Inflammation - Mechanisms of Disease - Cell Injury, Death, & Repair; Acute & Chronic Inflammation Flashcards
(198 cards)
1
Q
The etiology of disease refers to what?
A
The cause
2
Q
Identify the defined term: ____________ changes.
“Structural alterations in tissues or cells, recognized by gross and microscopic exam.”
A
Morphologic
3
Q
What is the initial cellular response to stress?
What occurs if the stress is excessive or prolonged?
A
Cell adaptation;
cell injury
4
Q
The hallmarks of reversible cell injury are:
_________ oxidative phosphorylation
_________ depletion
Cellular _________
A
The hallmarks of reversible cell injury are:
Reduced oxidative phosphorylation
ATP depletion
Cellular swelling
5
Q
The hallmarks of reversible cell injury are:
Reduced ________
ATP ________
________ swelling
A
The hallmarks of reversible cell injury are:
Reduced oxidative phosphorylation
ATP depletion
Cellular swelling
6
Q
What two signs of reversible cellular injury are visible under light microscopy?
A
Cellular swelling;
fatty change
7
Q
Name some of the ultrastructural signs of reversible cell injury in regards to the following cellular structures:
Plasma membrane
Mitochondria
ER
Nucleus
A
Plasma membrane - blebbing / microvilli loss / blunting
Mitochondria - swelling / amorphous densities
ER - dilation
Nucleus - granular and fibrillar disaggregation
8
Q
Are the following examples of cellular adaptations to reversible or irreversible injury?
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
A
Reversible
9
Q
The cellular adaptation hypertrophy is typically seen in stressed cells that no longer _________.
A
Divide
10
Q
What tissue adaptation is characterized in this endometrial micrograph?
A
Hyperplasia
(normal endometrium shown below)
11
Q
Hypertrophy is typically caused by an increase in cellular _________ synthesis.
Atrophy is typically caused by a decrease in cellular _________ synthesis an an increase in cellular _________.
A
Protein;
protein, proteolysis
12
Q
What is the typical, generic stimulus for metaplastic tissue change?
A
Chronic irritation
13
Q
Metaplastic tissue changes may predipose to _________ changes.
What is an example of this?
A
Neoplastic;
Barrett’s esophagus
(metaplasia predisposes to esophageal adenocarcinoma)
14
Q
An injurious stimulus may lead to reversible cellular changes.
Irreversible cell injury will occur if the stimulus is ________ and/or ________.
A
Excessive, prolonged
15
Q
What are some potential causes of tissue atrophy?
A
Loss of innervation or blood supply;
underusage;
loss of nutrition or endocrine stimulation;
pressure
16
Q
What ultrastructural marker of irreversible cell injury is shown in this electron micrograph?
A
Myelin figures
(whorled phospholipid masses derived from damaged cell membranes)
17
Q
What ultrastructural marker of irreversible cell injury is shown in this electron micrograph?
A
Mitochondrial dilation + amorphous densities (precipitated Ca2+ / globulins)
18
Q
What are the three nuclear changes (in order) of a cell undergoing irreversible cell injury (leading to necrosis)?
A
Pyknosis –> karryorhexis –> karyolysis
19
Q
In what order do the following nuclear changes occur in an irreversibly damaged cell undergoing necrosis?
Karryorhexis, Pyknosis, Karyolysis
A
Pyknosis –> Karryorhexis–>Karyolysis
20
Q
Define: pyknosis.
A
Shrunken, hyperchromatic nucleus
21
Q
Define: karryorhexis.
A
Nuclear fragmentation
22
Q
Define: karyolysis.
A
Fading of the nucleus
23
Q
True/False.
Apoptotic nuclear changes are as follows:
Pyknosis –> Karryorhexis –> Karyolysis
A
False.
Necrotic nuclear changes are as follows:
Pyknosis –> Karryorhexis –> Karyolysis
24
Q
How does apoptosis affect the nucleus?
A
Fragmentation into nucleosome-like fragments
25
In apoptosis, the plasma membrane is __________ and cellular contents are \_\_\_\_\_\_\_\_\_\_.
In necrosis, the plasma membrane is __________ and cellular contents are \_\_\_\_\_\_\_\_\_\_.
Intact, contained;
disrupted, released
26
Which of the following (or both) are characterized by frequent cases of adjacent inflammation?
(I.e. the process damages surrounding tissues.)
**Apoptosis**
**Necrosis**
Necrosis _only_
27
Which of the following (or both) are sometimes normal during physiological processes?
(I.e. non-pathological)
**Apoptosis**
**Necrosis**
Apoptosis _only_
28
Describe the basic cellular changes of apoptosis.
29
Describe the basic cellular changes of necrosis.
30
What nuclear change is displayed in this micrograph?
Pyknosis
| (shrunken, hyperchromatic)
31
What nuclear change is displayed in this micrograph?
Karyorrhexis
| (fragmentation)
32
This micrograph displays a normal renal tubule. How might a necrotic tubule appear?
33
What are the five main types of necrosis?
Coagulative,
liquefactive,
caseous,
fat,
fibrinoid
34
**Ischemia** in any tissue except the brain will cause what type of necrosis?
Coagulative necrosis
35
What kind of situations are most likely to cause liquefactive necrosis?
Brain ischemia,
abcesses
36
What is the main difference between coagulative and liquefactive necrosis?
Tissue architecture preserved in coagulative necrosis
(protein denaturation leads to decreased proteolytic activity)
37
What type of necrosis is characteristic of TB infection?
Caseous necrosis
38
What type of necrosis is characterized by saponification of lipids by calcium?
Fat necrosis
39
Saponification occurs in fat necrosis and is due to ___ reacting with free fatty acids.
Ca2+
40
Fibrinoid necrosis involves immune antigen-antibody complexes in the ________________ combining with fibrin.
Blood vessels
41
\_\_\_\_\_\_\_\_\_\_\_ necrosis involves immune antigen-antibody complexes combining with fibrin in the blood vessels.
Fibrinoid
42
Name the type of necrosis indicated in each of the following cases:
## Footnote
**Ischemic non-neural tissue**
**Blood vessel immune reaction**
**Abcess**
Coagulative
Fibrinoid
Liquefactive
43
Name the type of necrosis indicated in each of the following cases:
## Footnote
**Tuberculosis**
**Ischemic neural tissue**
**Pancreatic autodigestion**
Caseous
Liquefactive
Fat
44
Which type of necrosis is immune in nature?
Which type of necrosis preserves tissue architecture?
Fibrinoid;
coagulative
45
Why does coagulative necrosis preserve tissue architecture?
Protein denaturation --\> decreased proteolysis
46
What are apoptotic bodies?
Fragments of nucleus/cytoplasm
47
What is happening to this prominent epidermal cell?
Apoptosis
| (cellular swelling + dense cytoplasm)
48
**True/False**.
Apoptosis is only caused by normal physiologic stimuli.
**False**.
*DNA damage, misfolded proteins, certain infections,* and *glandular duct destruction* are all examples of potential pathologic causes of apoptosis.
49
Injurious cellular stressors such as UV rays, heat, and ROS can all trigger apoptosis via accumulation of what?
Misfolded proteins
## Footnote
*(and other damaged cellular contents; e.g., lipids and DNA)*
50
What are the two main pathways of apoptosis initiation?
**Mitochondrial** (intrinsic);
**death receptor** (extrinsic)
51
What is the main anti-apoptotic protein that maintains most cells?
Bcl-2
52
What proteins sense cellular stress?
What channel do they activate if the stress is excessive? (Where?)
**Bim**, **Bid**, **Bad** (BH3 family);
**Bax/Bak** (mitochondrial pores)
53
What is the end result of this pathway:
**Excessive cell stress** --\>
**BH3 family activated (Bim, Bid, Bad)** --\>
**Bax/Bak activated** --\>
**???**
Mitochondrial channels formed --\>
cytochrome C released --\>
**caspases activated** --\>
_apoptosis_
(*Note: this is the intrinsic pathway of apoptosis*)
54
Activation of what protein type is the end result of both the intrinsic and extrinsic pathways of apoptosis?
Caspases
55
What do caspases do?
Degrade the nuclear matrix --\> fragmentation
56
What are the two main triggers for the surface membrane death receptors of the extrinsic pathway of apoptosis?
TNF;
Fas-L
57
What process is basically programmed necrosis and resembles necrosis morphologically and apoptosis mechanistically?
Necroptosis
58
Is necroptosis dependent on caspases?
What complexes control the process?
No;
RIP1 / RIP3
59
How does the RIP1/RIP3 complex induce necroptosis?
Reduced ATP --\> increased ROS production --\> rupture of lysosomal membranes
60
**True/False**.
Necroptosis is programmed cell death that results in a non-inflammatory reaction resembling necrosis.
**False**.
Necroptosis is programmed cell death that results in an ***inflammatory*** reaction resembling necrosis.
61
Define: pyroptosis.
Infected cells activate caspase-1
| (infection-induced apoptosis)
62
**True/False**.
Increases in intracellular Ca2+ can cause decreased mitochondrial permeability and decreased cellular enzyme activity.
**False**.
Increases in intracellular Ca2+ can cause ***increased*** mitochondrial permeability and ***increased*** cellular enzyme activity.
63
Mitochondrial damage leads to leakage of pro-\_\_\_\_\_\_\_\_\_\_\_ proteins.
Apoptotic
64
Why is lysosomal damage dangerous to cell survival?
Release of lytic enzymes
65
Explain why ATP depletion causes the following cellular effects:
## Footnote
**Cell / ER swelling**
**Chromatin clumping**
**Lipid accumulation / protein depletion**
**Decreased Na/K ATPase activity** (cell / ER swelling)
**Lactic acidosis** (chromatin clumping)
**Ribosomal detachment** (lipid accumulation / protein depletion)
66
What are the three main damaging effects of ROS?
Protein/enzyme misfolding,
membrane disruption,
DNA damage
67
Define: autophagy (a form of cell death).
A non-apoptotic, non-necrotic form of cellular recycling
(the cells are scrapped for parts/nutrients)
68
Why can excessive/prolonged Ca2+ influx be damaging to cell survival?
**Enzymatic activation**
*(e.g. proteases, phospholipases, phosphatases, glucosidases, ATPases, RNases, DNases, etc.)*
69
Where are pro-apoptotic protein clusters (e.g. cytochrome *C*) contained within the mitochondria?
The intermembrane space
70
What are the main serum markers for cardiac injury?
And bile duct epithelial injury?
And hepatic injury?
CK-MB, troponins;
ALP;
AST, ALT
71
Describe the pathophysiology of ischemia-reperfusion injury.
**Increased [ROS] and [RNS]** --\> increased inflammation / complement activation
72
What are some examples of categories of materials that can accumulate in a cell?
**Energy storage** (e.g. lipids, glycogen);
**misfolded proteins** (e.g. amyloid, α1-antitrypsin);
**endogenous** (e.g. lipofuscin or due to lysosomal storage diseases);
**exogenous** (e.g. heavy metals)
73
Dystrophic calcification occurs in __________ tissues when calcium levels are \_\_\_\_\_\_\_\_\_\_.
Damaged;
normal
74
Metastatic calcification occurs in __________ tissues when calcium levels are \_\_\_\_\_\_\_\_\_\_.
Normal;
elevated (e.g. PTH excess)
75
Nephrocalcinosis is an example of ___________ (dystrophic/metastatic) calcification.
Metastatic
| (due to elevated calcium levels)
76
\_\_\_\_\_\_\_\_\_\_ calcification occurs in normal tissues when serum calcium levels are significantly elevated.
Metastatic
77
\_\_\_\_\_\_\_\_\_\_ calcification occurs in damaged tissues when serum calcium levels are normal.
Dystrophic
78
What body areas are most likely to be affected by metastatic calcification?
Areas of acid secretion
(e.g. gastric mucosa, kidneys, lungs, blood vessels)
79
A calcified aortic valve is an example of what kind of calcification?
Dystrophic
| (as opposed to metastatic)
80
What are the cardinal S/Sy of inflammation?
**Pain** (dolor),
**redness** (rubor),
**loss of function** (functio laesa),
**swelling** (tumor),
**heat** (calor)
81
What suffix signifies inflammation?
'-itis'
82
What is the purpose of inflammation?
To bring cells and molecules of host defense from the circulation to the sites where they are needed
83
How long does acute inflammation usually take to set in?
How long does it usually last?
Minutes;
hours to days
84
What are the major steps of inflammation according to accomplished function?
1. Increase in blood vessel permeability
2. Leukocyte chemotaxis
3. Leukocyte activation
85
What main substance is released in acute inflammatory situations by endothelial cells to promote vasodilation?
How long is its half-life?
Nitric oxide;
seconds
86
In acute inflammatory settings, nitric oxide is secreted by _____________ cells to promote \_\_\_\_\_\_\_\_\_\_\_\_\_.
Endotheilal;
vasodilation
87
What main substance is released in acute inflammatory situations by mast cells / basophils / platelets to promote an increase in vascular permeability (and vasodilation)?
Histamine
88
In acute inflammatory settings, histamine is secreted by _____________ cells to promote \_\_\_\_\_\_\_\_\_\_\_\_\_.
Mast cells / basophils / platelets;
vascular permeability / vasodilation
89
What substance is the major mediator of vasodilation in acute inflammation?
What substance is the major mediator of vascular permeability in acute inflammation?
Nitric oxide;
histamine
90
**True/False**.
All of the following are examples of stimuli that cause mast cell degranulation:
**Trauma, cold, heat, allergic reactions, anaphylatoxins C3a and C5a, other histamine-releasing proteins, neuropeptides** (e.g., substance P), **and cytokines IL-1 / IL-8**
True.
91
Histamine results in dilation of __________ and increased permeability of \_\_\_\_\_\_\_\_\_\_.
Arterioles;
venules
92
What happens rapidly to endothelial cells in cases of acute inflammation and typically lasts for 15 - 30 min?
Endothelial contraction
93
Besides endothelial contraction, what are some other processes that increase the inter-endothelial space?
Endothelial damage (direct or leukocyte-mediated);
increased transcytosis
94
**True/False**.
Lymphatic vessels proliferate during acute inflammation.
True.
95
Upon examining a patient's swollen forearm, you notice red streaks on the patient's skin radiating outwards away from a purulent sore.
What is causing the red streaks?
Lymphangitis
96
What term refers to inflammation of the lymph nodes?
What term refers to inflammation of the lymph vessels?
Lymphadenitis;
lymphangitis
97
What are the two general types of edematous fluid?
Put the higher osmolality one first.
Exudate;
transudate
98
Transudate is edematous fluid characterized by ___ protein content and ___ specific gravity.
Low;
low
99
Ascites is an example of what type of fluid?
A pus-laden plural effusion is an example of what type of fluid?
Transudate;
exudate
100
The steps of leukocyte recruitment are the following:
1. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
2. Extravasation (diapedesis).
3. In-tissue chemotaxis.
The steps of leukocyte recruitment are the following:
1. **Margination, rolling, & adhesion to endothelium**.
2. Extravasation (diapedesis).
3. In-tissue chemotaxis.
101
The steps of leukocyte recruitment are the following:
1. Margination, rolling, & adhesion to endothelium.
2. \_\_\_\_\_\_\_\_\_\_\_\_\_\_.
3. In-tissue \_\_\_\_\_\_\_\_\_\_\_.
The steps of leukocyte recruitment are the following:
1. Margination, rolling, & adhesion to endothelium.
2. **Extravasation** (diapedesis).
3. In-tissue **chemotaxis**.
102
What is leukocyte margination?
Leukocytes moving to vessel wall
103
After marginating to the endothelium, via what endothelial proteins do leukocytes begin to roll? Be specific.
**E-selectins** (endothelium),
**P-selectins** (endothelium & platelets),
**L-selectins** (leukocytes)
104
**True/False**.
Endothelial selectins bind X-modified integrins on leukocyte surfaces.
**False**.
Endothelial selectins bind X-modified ***Sialyl-Lewis glycoproteins*** on leukocyte surfaces.
105
What are Weibel-Palade bodies?
What causes their release to the cell surface?
**P-selectin** granules (in endothelial cells);
histamine, thrombin, and platelet-activating factor
106
**True/False**.
The cytokines **TNF** and **IL-1** increase the expression of selectins and their ligands on endothelial cells and leukocytes.
True.
107
Leukocyte rolling causes what to occur for leukocytes?
Slowing down / stronger endothelial binding
108
**Chemokines** increase leukocyte adhesion by converting (1) __________ to a high-affinity state.
**Cytokines** such as IL-\_\_ and ___ induce endothelial VCAM-1 and ICAM-1 expression for the (1) __________ to bind.
(1) Integrins;
IL-1, TNF
109
**True/False**.
Leukocyte CAMs bind endothelial integrins during leukocyte adhesion.
**False**.
Leukocyte _integrins_ bind endothelial _CAM__s_ during leukocyte adhesion.
110
Name where each of the following are found, respectively:
E-selectins
P-selectins
L-selectins
E-selectins --- **e**ndothelium
P-selectins --- **p**latelets; endothelium
L-selectins --- **l**eukocytes
111
The cytokines of acute inflammation mainly increase the expression of endothelial adhesion molecules such as ___________ and \_\_\_\_\_\_\_\_\_\_\_.
The cytokines of chronic inflammation mainly increase the expression of enzymes associated with ___________ remodeling and \_\_\_\_\_\_\_\_\_\_\_.
Selectins, integrins;
matrix, thrombogenicity
112
\_\_\_, IL-\_\_, and IL-\_\_ are major mediators of acute inflammation.
IFN-\_\_, IL-\_\_, and IL-\_\_ are major mediators of chronic inflammation.
TNF, 1, 6;
γ, 2, 17
113
How are chemokines grouped?
## Footnote
**α**
**β**
**γ**
According to conserved cysteine (C) residues
α - **C-X-C**
β - **C-C**
γ - **C**
114
What do cell type(s) do each of the following chemokine groups act on, respectively?
α (C-X-C)
β (C-C)
γ (C)
α (C-X-C) - mostly **neutrophils**
β (C-C) - attract **monocytes**, **eosinophils**, **basophils**, and **lymphocytes**
γ (C) - specific for **lymphocytes**
115
What chemokine promotes strong adhesion of monocytes and T cells to endothelial cells?
CX3C (fractalkine)
116
**True/False**.
Chemokine receptors are mostly tyrosine kinase receptors.
CXCR-4 and CCR-5 are involved in ____ infection.
**False**.
Chemokine receptors are mostly ***GPCRs***.
CXCR-4 and CCR-5 are involved in **HIV** infection.
117
Endothelial P- and E-selectins are involved in leukocyte \_\_\_\_\_\_\_\_\_\_\_\_.
Endothelial ICAM-1 and VCAM-1 are involved in leukocyte \_\_\_\_\_\_\_\_\_\_\_\_.
Rolling;
adhesion
118
\_\_\_\_\_\_\_\_\_\_\_\_ P- and E-selectins are involved in leukocyte rolling.
\_\_\_\_\_\_\_\_\_\_\_\_ sialyl-Lewis X-modified proteins are involved in leukocyte rolling.
Endothelial;
leukocyte
119
\_\_\_\_\_\_\_\_\_\_\_\_\_integrins are involved in leukocyte adhesion.
\_\_\_\_\_\_\_\_\_\_\_\_\_ ICAM-1 and VCAM-1 are involved in leukocyte adhesion.
Leukocyte;
endothelial
120
What are the endogenous and exogenous agents of chemotaxis?
Endogenous --- **Cyto/chemokines, complement, arachidonic acid metabolites**
Exogenous --- **Bacterial products**
121
How does chemotaxis work on a cellular level?
(I.e., what do the signals induce at the front and back of the cell?)
_Front_: **actin** polymerization
_Back_: **myosin** filament localization
122
What is the timeline of the following pieces in acute inflammation?
## Footnote
**Neutrophil**
**Monocyte/Macrophages**
**Edema**
**\< 1 day** --\> Edema
**6 - 24 hours** --\> Neutrophils
**~2 days** --\> Monocytes/macrophages
123
Some ___________ infections produce continous recruitment of neutrophils for several days.
\_\_\_\_\_\_\_\_ infections tend to have more lymphocytes
Bacterial;
viral
124
How do leukocyte intracellular conditions change when they become activated?
**Increased** cytosolic **calcium**;
enzyme activation / ROS production
125
What are the steps of phagocytosis?
1) ___________ and attachment of particle to be ingested by the leukocyte
2) ___________ with subsequent formation of phagocytic vacuole
3) ___________ of the ingested material
Recognition;
engulfment;
degradation
126
Name a few of the recognition/attachment receptors of phagocytosis.
* **Macrophage mannose** receptors
* **Scavenger** receptors
* **Macrophage integrins**
* Receptors for **opsonins**
127
Neutrophils use the ____________ to create ROS in order to destroy phagocytosed materials.
Respiratory burst
128
What are the intermediates of the respiratory burst?
**O2** --\> **O2-** --\> **H2O2** --\> **ClO-**
(Oxygen --\> superoxide --\> hydrogen peroxide --\> hypochlorite)
129
What are the enzymes of the respiratory burst?
**NADPH oxidase** (O2 --\> O2-);
**superoxide dismutase** (O2- --\> H2O2);
**myeloperoxidase** (H2O2 --\> ClO-)
130
What defect causes leukocyte adhesion deficiency type I (a cause of recurrent bacterial infections)?
**β2**
| (shared by LFA-1 and Mac-1 integrins)
131
What defect causes leukocyte adhesion deficiency type II (a cause of recurrent bacterial infections)?
**Sialyl-Lewis X**
(E- and P-selectins ligand)
(may be a defect of fucosyl transferase)
132
The basic cause of Chediak-Higashi syndrome is defective fusion of __________ with \_\_\_\_\_\_\_\_\_.
Phagosomes;
lysosomes
133
What enzyme is deficient in chronic granulomatous disease?
What is the most common inheritance?
NADPH oxidase;
X-linked
134
What type of cell is especially rich in inflammatory responses in chronic granulomatous disease?
Macrophages
| (neutrophil response is inadequate)
135
Leukocyte adhesion deficiency I and II, Chediak-Higashi syndrome, and chronic granulomatous disease are all characterized by recurrent _______________ infections.
Bacterial
136
Name a few examples of conditions that might induce leukocyte dysfunction.
Chemotherapy;
leukemia;
diabetes;
dialysis
137
The effects of acute inflammation include:
**fever, leukocytosis and left shift, chills, malaise**
This is mainly due to what two factors?
**IL-1**, **TNF**
| (also IL-6, CRP, hepcidin, fibrinogen)
138
Bacterial infections cause \_\_\_\_\_\_\_\_ia.
Viral infections cause \_\_\_\_\_\_\_osis.
Parasites, allergies, and asthma cause \_\_\_\_\_\_\_\_ia.
Bacterial infections cause **netrophil**ia.
Viral infections cause **leukocyt**osis.
Parasites, allergies, and asthma cause **eosinophil**ia.
139
**True/False**.
Septic shock is mainly mediated by IL-2 and CRP.
**True/False**.
Septic shock is mainly mediated by **IL-1** and **TNF**.
140
What is the difference between septic shock and systemic inflammatory response syndrome (SIRS)?
SIRS is due to **non-infectious causes**
141
**True/False**.
Neutrophils and the mediators of acute inflammation have short half-lives.
True.
142
When acute inflammation has ended, the pro-inflammatory signals switch to what?
Anti-inflammatory signals
143
\_\_\_\_\_\_\_\_\_\_\_\_\_ inflammatory fluid occurs in effusions and blisters.
Serous
144
\_\_\_\_\_\_\_\_\_\_\_\_\_ inflammatory fluid occurs in inflammation of body cavities (e.g. meninges, pericardium, pleura).
Fibrinous
145
\_\_\_\_\_\_\_\_\_\_\_\_\_ inflammatory fluid occurs in inflammation that produces pus.
It is typically of a bacterial origin.
Suppurative (purulent)
146
An abcess is a localized collection of ____________ tissue surrounded by a zone of viable \_\_\_\_\_\_\_\_\_\_\_\_.
Purulent (suppurative);
neutrophils
147
An ulcer is a local defect of the surface tissue with the co-existence of _______ and _______ inflammation, with potential scar formation.
Acute;
chronic
148
**True/False**.
Chronic inflammation always follows acute inflammation.
**False**.
Chronic inflammation can arise insidiously.
149
How long does chronic inflammation last?
Weeks or months
150
Acute inflammation is mostly managed by what cell type(s)?
Chronic inflammation is mostly managed by what cell type(s)?
Neutrophils;
macrophages, lymphocytes, plasma cells
151
Angiogenesis and fibrosis are attempts at healing seen in ________ inflammation.
Chronic
152
What type of pulmonary inflammation is shown here?
(Acute or chronic?)
Acute
153
What type of pulmonary inflammation is shown here?
(Acute or chronic?)
Chronic
154
What is the half-life of macrophages in circulation?
And in tissues?
1 day;
months-to-years
155
Which of the following would NOT be a significant component of a typical chronic inflammatory process?
## Footnote
**A. Lymphoid follicles**
**B. Plasma cells**
**C. Neutrophils**
**D. Macrophages**
C. Neutrophils
156
The two types of macrophage activation are the _________ pathway and the _________ pathway.
Classical;
alternative
157
What is the difference in macrophage function between the classical and alternative activation pathways?
**Inflammation** (classical);
**repair** (alternative)
158
What cytokines cause classical macrophage activation?
IFN-γ; microbes
159
What cytokines cause alternative macrophage activation?
IL-4;
IL-13
160
**True/False**.
The adaptive immune system has little-to-no role in chronic inflammation.
**False**.
CD4+ T cells and B cells play prominent roles.
161
What are the two most basic causes of granulomatous inflammation?
Foreign bodies (foreign body granulomas);
a difficult inciting agent to eradicate (immune granulomas)
162
Epithelioid and giant cells are very common in _____________ granulomas.
Persistent T cell-mediated immune activity is characteristic of _____________ granulomas.
Foreign body;
immune
163
What are the two methods of tissue repair?
Which is characteristic of wound healing?
Which is characteristic of chronic inflammation?
Which is characteristic of epithelial tissues?
Regeneration, scar formation;
scar;
scar;
regeneration
164
Which of these tissues are stable tissues (as opposed to labile or permanent)?
## Footnote
**Kidney**
**Pancreas**
**Adrenal**
**Lung**
**Endothelial cells**
All of them
165
Which tissue type is the most important tissue source of growth factors?
Which cell type is the most important cellular source of growth factors?
ECM;
macrophages
166
How long does it take for a liver remnant to double after 60% of the liver is resected?
1 month
167
What mediators of chronic inflammation are produced following stimulation by the following mediators of acute inflammation?
IL-6
IL-1 and TNF
IL-6 --\> **CRP** and **fibrinogen**
IL-1 and TNF --\> **serum amyloid A**
168
What are the effects of elevated CRP, fibrinogen, and serum amyloid A on tissues (due to chronic inflammation)?
CRP / fibrinogen --\> elevated ESR;
SAA --\> amyloidosis (in severe cases)
169
Inflammation causes a _____ shift leukocytosis.
Left
170
What are some of the systemic effects of septic shock due to elevated TNF and IL-1?
**1.** _________ in blood pressure
**2.** D\_\_\_\_\_\_\_\_\_\_ i\_\_\_\_\_\_\_\_\_\_ c\_\_\_\_\_\_\_\_\_\_
**3.** __________ abnormalities (e.g. insulin resistance, hyperglycemia)
**1. Decrease** in blood pressure
**2. Disseminated intravascular coagulation**
**3. Metabolic** abnormalities (e.g. insulin resistance, hyperglycemia)
171
What growth factors are involved in angiogenesis?
VEGF;
FGFs;
angiopoeitins I and II
172
**True/False**.
Angiogenesis requires both extensive endothelial-ECM interactions and also ECM destruction by metalloprotease activity.
True.
173
What are the two main forms of angiogenesis?
From pre-existing vessels;
de novo
174
Name some of the systemic effects associated with acute phase inflammatory responses.
**Elevated** heart rate, BP, and temperature;
**decreased** sweating;
**presence of** chills, rigors, anorexia, malaise, somnolence
175
What are the two forms of tissue healing?
Tissue regeneration;
scar formation
176
Scar formation involves the following processes:
## Footnote
**\_\_\_\_\_\_\_genesis.**
**Formation of ________ tissue.**
**Remodeling of ________ tissue.**
Scar formation involves the following processes:
**Angio**genesis.
Formation of **granulation** tissue.
Remodeling of **connective** tissue.
177
\_\_\_\_\_\_ is produced by cells in granulation tissue and acts to increase collagen/fibronectin synthesis and decrease metalloprotease activity.
**TGF-β** is produced by cells in granulation tissue and acts to increase collagen/fibronectin synthesis and decrease metalloprotease activity.
178
Is this granulation tissue or a mature scar?
Granulation tissue
(mature scar below)
179
**True/False**.
_All_ of the following points describe metalloproteases.
1. ECM-degrading.
2. Copper-dependent.
3. Produced by fibroblasts only.
4. Released as zymogens.
**False**.
All of the following points describe metalloproteases:
1. ECM-degrading
2. ***Zinc***-dependent.
3. Produced by ***neutrophils, synovial cells, fibroblasts, and macrophages, and some epithelial cells***.
4. Released as zymogens.
180
How do vascular regression and fibroblast differentiation (into myofibroblasts) promote scar maturation?
Scar contraction
181
Which of the following can delay wound healing?
## Footnote
**Glucocorticoids**
**Diabetes mellitus**
**Vitamin deficiencies (e.g. vitamin C)**
**Poor perfusion**
**Foreign bodies**
All of them
182
Healing of _primary intention_ involves reconnection of the superficial _________ cutaneous layer by \_\_\_\_\_\_\_\_\_\_.
Healing of _primary intention_ involves reconnection of the superficial **epithelial** cutaneous layer by **regeneration**.
183
Healing of ________ intention involves reconnection of the superficial epithelial cutaneous layer by regeneration.
Healing of **primary** intention involves reconnection of the superficial epithelial cutaneous layer by regeneration.
184
Describe the time frame for the following processes that occur after a cutaneous injury:
## Footnote
**- Clot formation / Neutrophil entry into wound -**
**- Macrophage entry into wound / angiogenesis / granulation tissue formation -**
**- Scab removal / healed surface / no inflammation -**
- 24 hours -
- 3 - 7 days -
- Weeks -
185
How long will it take most cutaneous scars to make it back to 100% of the tensile strength the skin held before injury?
Never
186
Healing of _________ intention is used for less extensive tissue loss/destruction when the normal edges can still be approximated.
Healing of _________ intention is used for more extensive tissue loss/destruction when the normal edges cannot still be approximated.
Healing of **primary** intention is used for less extensive tissue loss/destruction when the normal edges can still be approximated.
Healing of **secondary** intention is used for more extensive tissue loss/destruction when the normal edges cannot still be approximated.
187
In what way are the components of healing by secondary intention significantly different from healing by primary intention?
Quantity
## Footnote
*(larger clot, more debris, more inflammation, more time, larger scar)*
188
Initial granulation tissue is made of type ___ collagen.
This is replaced by type ___ collagen at ~\_\_ weeks.
Initial granulation tissue is made of type **III** collagen.
This is replaced by type **I** collagen at ~**2** weeks.
189
Granulation tissue _______ (is/is not) vascular.
Granulation tissue **is** vascular.
190
What is the main cell type that causes wound contracture?
Myofibroblasts
191
**True/False**.
Over the first six weeks of healing, large skin wound contractures can lead to a reduction of 10-15% in the size of the healed area from original size.
**True**.
Over the first six weeks of healing, large skin wound contractures can lead to a reduction of 10-15% in the size of the healed area from original size.
192
After 1 week, wound strength is \_\_\_% of unwounded skin.
Plateaus at \_\_\_% after about 3 months.
After 1 week, wound strength is **10**% of unwounded skin.
Plateaus at **70-80**% after about 3 months.
193
After __ \_\_\_\_\_\_\_, wound strength is 10% of unwounded skin.
Plateaus at 70-80% after about __ \_\_\_\_\_\_\_.
After **1 week**, wound strength is 10% of unwounded skin.
Plateaus at 70-80% after about **3 months**.
194
\_\_\_\_\_\_\_\_ is to internal organs as scarring is to the skin.
**Fibrosis** is to internal organs as scarring is to the skin.
195
What term refers to wound rupture after partial healing?
Wound dehiscence
196
What is 'proudflesh?'
Excessive granulation tissue
## Footnote
*(forms large scar that does not reapproximate original skin surface)*
197
Match the following bolded terms with their respective italicized definitions:
**keloid**, **proudflesh**, **contractures**
*restricted movement due to wound tightening, excessive scarring, excessive granulation tissue*
**Keloid** - *excessive scarring*
**Proudflesh** - *excessive granulation tissue*
**Contractures** - *restricted movement due to wound tightening*
198
What cell type is most important in mediating wound healing?
What cell type is most important in the actual process of wound healing?
Macrophages;
fibroblasts
