Unit II Flashcards
1
Q
What is aplastic anemia?
A
Normocytic-normochromic anemia that results from a loss of blood cell precursors, causing hypoplasia of bone marrow, RBCs, WBCs, and platelets.
2
Q
What are the four classic signs of inflammation?
A
calor (heat), rubor (redness), tumor (swelling), and dolor (pain)
3
Q
What is the innate immune system?
A
nonspecific defense mechanism, immediately or very soon (minutes to hours) Includes physical barriers: skin, mediators in the blood, immune system cells
4
Q
What is the adaptive immune system?
A
antigen-specific response. More complex than innate. Requires antigen processing. Involves creating cells specifically designed for that antigen. Also includes memory for faster future encounters
5
Q
Signs of acute inflammation
A
rapid in onset and of short duration, lasting from a few minutes to as long as a few days, and is characterized by fluid and plasma protein exudation and a predominantly neutrophilic leukocyte accumulation.
6
Q
What are the cellular infiltrates for acute inflammation?
A
neutrophils
7
Q
Signs of Chronic inflammation
A
more insidious, is of longer duration (days to years), and is typified by influx of lymphocytes and macrophages with associated vascular proliferation and fibrosis (scarring).
8
Q
What are the cellular infiltrates for chronic inflammation?
A
lymphocytes and macrophages
9
Q
What are the agents that cause acute inflammation?
A
Infection, trauma, tissue necrosis, foreign material, and immune reactions
10
Q
What is the roll of toll like receptors?
A
Pattern recognition receptors found on the surface and within the host cell that can detect foreign material. Once activated it triggers the production of transcription factors to create proteins that mediate inflammation, interfere with action of infectious agents (interferons) and promote lymphocyte activation.
11
Q
What is an inflammasome?
A
receptors that stimulate inflammation via activation of caspase-1. Caspase-1 forms active Interleukin-1β (IL-1β), which then recruits leukocytes that come
in to clean up dead cells
**recognizes products of dead cells like ATP and free floating DNA
12
Q
inflammasome induce the secretion of what molecule?
A
Interleukin-1β
13
Q
What are exudates?
A
An exudate is formed in inflammation because vascular permeability increases as a result of the increase in interendothelial spaces.
**typical inflammation response
14
Q
What are transudates?
A
A transudate is formed when fluid leaks out because of increased hydrostatic pressure or decreased osmotic pressure.
**noninflammatory conditions/ vascular wall still in tact
15
Q
What are the two major changes during acute inflammation?
A
increased blood flow and increase vessel permeability
16
Q
What mechanism contribute to increase vessel permeability?
A
Endothelial cell contraction leading to intercellular gaps in postcapillary venules
Injury of endothelial cells –> incomplete endothelial layer
Transcytosis
17
Q
quick response endothelial contraction is stimulated by what molecules?
A
histamines
18
Q
Longer-term contraction is prompted by what molecules?
A
Cytokines like IL-1 and TNF
19
Q
What is fibrosis?
A
If the tissue cannot regenerate or if there has been significant tissue destruction then
instead connective tissue fills the void
20
Q
What adhesion molecules grab onto sugars that are present on the surface of leukocytes to promote leukocyte rolling?
A
P and E selectins
21
Q
What molecule stimulates P-selectins?
A
histamine
22
Q
What molecule stimulates E-selectins?
A
IL-1
23
Q
What is stasis?
A
caused when numerous dilated small vessels become packed with red blood cells and blood viscosity increases
24
Q
What is a low concentrations of protein and few or no blood cells in the extravascular space indicative of?
A
transudates
25
explain the adhesion process for leukocytes
When the adherent leukocytes encounter the displayed chemokines, the cells are activated, and their integrins undergo conformational changes and cluster together, thus converting to a high-affinity form
26
explain the adhesion process of endothelial cells
cytokines, notably TNF and IL-1 (also secreted at sites of infection and injury), activate endothelial cells to increase their expression of ligands for integrins. These ligands include intercellular adhesion molecule-1 (ICAM-1),
27
Where does diapedesis take place?
mainly in the venules of the systemic vasculature
28
what are opsonins?
Host proteins that coat microbes and target them for phagocytosis
29
Name examples of opsonins
IgG, compliment system (C3b), collectins
30
What are neutrophil extracellular traps?
tracellular fibrillar networks that are produced by neutrophils to prevent the spread of microbes.
Essentially they release their own chromatin to trap these microbes in place.
31
What collateral tissue damage is associated with inflammation?
1. Tissue surrounding infectious agents may become damaged.
2. Cleaning up necrotic tissue by the inflammatory process may cause additional damage
3. Inflammatory process is directed against host tissues (i.e. autoimmune diseases)
32
What are common causes for defective leukocyte function?
1. aplastic anemia secondary to chemotherapy
2. Diabetes
3. Chédiak-Higashi syndrome which has mutations in the proteins responsible for trafficking of
organelles; thus phagosomes and lysosomes cannot properly fuse.
33
What are the trademark cells for chronic inflammation?
monocytic cells - lymphocytes, macrophages, dendritic cells, plasma cells
34
What are the characteristics of chronic inflammation?
- inflammation with mononuclear cells
- tissue destruction
- repair
35
Describe a smear with acute inflammation of the lung
neutrophils filled in the alveolar space and blood vessel congestion
36
what is pruritus?
severe itching the skin
37
What are macrophages in the liver called?
Kupffer cells
38
What induces classical macrophage activation?
microbial products such as endotoxin, by T cell–derived signals, importantly the cytokine IFN-γ
39
What do classically activate macrophages produce?
NO, and ROS, all of which enhance their ability to kill ingested organisms, and secrete cytokines that stimulate inflammation
40
What induces alternative macrophage activation?
cytokines other than IFN-γ, such as IL-4 and IL-13, produced by T lymphocytes and other cells, including mast cells and eosinophils
41
What do alternative activated macrophages produce?
growth factors that promote angiogenesis, activate fibroblasts and stimulate collagen synthesis.
42
What is the principal role for alternative activated macrophages?
tissue repair, fibrosis, anti-inflammatory effects
43
What do TH1 CD4+ T lymphocytes secrete?
IFN-ɣ which activates classical pathway macrophages
44
What do TH2 CD4+ T lymphocytes secrete?
IL-4, IL-5, IL-13 which activates alternative pathway macrophages; also activates eosinophils
45
What do TH17 CD4+ T lymphocytes secrete? I
L-17 which recruits neutrophils and monocytes
46
Which chemokine recruits eosinophils?
eotaxins
47
What type of antibody is found on mast cells?
IGE
48
What cells are central players in allergic reactions, including anaphylactic shock?
IgE armed mast cells
49
What is the characteristic of granulomatous inflammation?
aggregates of activated enlarged macrophages with scattered lymphocytes
50
What is the prototype of a granulomatous disease?
tuberculosis
51
What are diseases associated with Granulomatous inflammation?
Crohn's disease and sarcoidosis
52
what are the cells of chronic inflammation?
Macrophages
Lymphocytes
Eosinophils
Mast cells
53
What are the cytokines associated with acute phase reaction aka systemic inflammation?
TNF, IL-1, and IL-6 are responsible for many of the systemic effects
54
what cells produces the cytokines associated with acute phase reaction?
leukocytes
55
What triggers a fever?
a response to substances called pyrogens that act by stimulating prostaglandin synthesis in the vascular and perivascular cells of the hypothalamus.
56
what is the role of IL-6 in acute phase reactions?
IL-6 stimulates the hepatic synthesis of a number of plasma proteins
57
What are the acute phase proteins?
C-reactive protein (CRP) and serum amyloid A (SAA) protein are known to adhere to cell walls and may act as opsonins
58
What is used to test for the presence of inflammation?
erythrocyte sedimentation rate (ESR)
Fibrinogen binds red blood cells causing them to form stacks that quickly form sediments
59
What cytokine cause an increased number of immature white blood cells (early release)?
TNF and IL-1
60
What infection is assocaited to neutrophilia?
Bacterial infection
61
What infection is associated with lymphocytosis?
viral infection
62
What infection is associated with eosinophilia?
asthma and parasitic infection
63
What infection is associated with leukopenia?
specific infection like typhoid fever
64
What triggers the production of leukocytes?
colony stimulating factor
65
What are the two vasoactive amines and where are they stored?
histamine and serotinin both stored in mast cells
66
What is the role of histamine?
arterial dilation and & endothelial contraction
67
What is the role of serotonin?
vasoconstriction to aid in clotting
68
Where is serotonin found?
in platelet granules that are released during platelet aggregations
69
What stimuli cause mast cells to release histamine?
```
Physical features - trauma or heat
Immune – Binding of IgE
Compliment (C3a, C5a)
Histamine releasing proteins (from leukocytes)
Neuropeptides
Cytokines (IL-1, IL-8)
```
70
name of the source of arachidonic acid metabolites
Leukocytes, mast cells, endothelium & platelets
71
how are AA metabolites inactivated?
by spontaneous decay and enzymes
72
What are the two major pathways of arachidonic acid metabolism?
cyclooxygenase and lipoxygenase pathway
73
The cyclooxygenase pathway leads to what products?
prostaglandins and thromboxanes
74
What is the role of prostaglandins?
causes vasodilation and inhibits platelet aggregation
75
What is the role of thromboxanes?
causes vasoconstriction and promotes platelet aggregation
76
The lipoxygenase pathway leads to what products?
leukotrienes and lipoxins
77
What is the role of leukotrienes?
causes bronchoconstriction and increased vascular permeability
78
What is the role of lipoxins?
inhibit neutrophil chemotaxis and adhesion to endothelium and thus serve as endogenous **antagonist of leukotrienes.
79
What medication would you use to block the cyclooxygenase pathway?
NSAIDs
80
What medication would you use to block the entire arachidonic acid metabolites?
glucocorticoid steroids
81
What enzyme does glucocorticoid sterioids inhibit?
phospholipase
**stops the release of all AA metabolites
82
What cell derived mediator contributes to pain and fever?
prostaglandins
83
What is platelet activating factor?
phospholipid-derived mediator with a broad spectrum of inflammatory effects.
Effects include: platelet aggregation, vasodilation, vascular permeability and bronchoconstriction along with stimulation of platelets and cells to form other mediators
84
What are important acute inflammatory cytokines?
TNF, IL-1, IL-6
85
What are the main functions of TNF and IL-1?
Cause endothelial activation (leukocyte binding and recruitment)
Also induce systemic effects of inflammation: Fever, acute phase protein synthesis, etc
86
What are the important chronic inflammatory cytokines?
IFN-γ and IL-12
87
What is the role of IFN-γ?
Stimulates classical macrophage activation
88
What is the role of IL-12?
Stimulate the growth and function of T cells
89
What induces the activation of IL-1?
inflammasome
90
What cells produce reactive oxygen species?
neutrophils and macrophages
91
What is the role of reactive oxygen species?
highly toxic oxidizers that not only damage microbes, but also host tissues
92
What is the function of nitric oxide in inflammation?
a free radical that can be used to kill microbes
| A mediator of vasodilation, antagonizes platelet activation, & reduces leukocyte recruitment
93
How is Type II NOS stimulated?
induced in macrophages and endothelial cells
| Induced by IL-1, TNF, IFN-γ and bacterial endotoxins
94
What pH conditions are ideal for intracellular lysosomal enzymes?
low pH
95
What pH conditions are ideal for extracellular lysosomal enzymes?
neutral pH
96
What is the role of alpha 1- antitripsin?
inhibits elastase **protease inhibitor
97
What is the role of alpha 2-macroglobulin
inhibits a large variety of proteinases (e.g. collagenase)
98
Give an example of a neuropeptide
Substance P, an 11 amino acid peptide
Secreted by nerves and inflammatory cells (macrophages, eosinophils, lymphocytes, dendritic cells)
**generates proinflammatory effects in immune and epithelial cells
99
What are neuropeptides active in?
vascular tone and permeability
100
What is the central complement factor?
C3
101
What are they three pathways for the formation of C3?
1) the classical pathway, triggered by fixation of the first complement component C1 to antigen-antibody complexes;
(2) the alternative pathway, triggered by bacterial polysaccharides (e.g., endotoxin)
(3) the lectin pathway, in which a plasma lectin binds to mannose residues on microbes and activates an early component of the classical pathway (but in the absence of antibodies).
102
What happens once C3 is cleaved?
It cleaves into C3a and B. C3b deposits on the cell or microbial surface where complement was activated and then binds to the C3 convertase complex to form C5 convertase; this complex cleaves C5 to generate C5a and C5b and initiate the final stages of assembly of C6 to C9.
103
What is the role of C3a and C5a?
increases vascular permeability and stimulates mast cells to release histamine
104
What complement molecule activates the lipogenous pathway for AA metabolism?
C5a
105
What complement molecules activate leukocytes increasing their endothelial adhesion?
C5a, C4a, C3a
**these are also chemotatic agents for neuts, eos, basophils and monocytes
106
What complement molecule acts as opsonin for enhanced phagocytosis?
C3b
107
What part of complement forms the MAC?
multiple C9 proteins
108
What protects host tissue from activated complement?
C1 inhibitor blocks activation of C1
| **Decay-accelerating factor (DAF) and **factor H limit C3/C5 convertase formation
109
What is the role of clotting factor XII in inflammation?
important clotting factor that activates the kinin system --> ultimately leads to bradykinin which increases vascular permeability, vascular dilation and pain
110
What activates factor XII?
Intermediate product Kallikrein is chemotatic and activates Factor XII
111
what molecule down regulates macrophages?
IL-10
112
what molecule promotes fibrosis and is anti-inflammatory?
TGF-beta
113
What are the two main types of tissue repair?
Regeneration and scar formation
114
What cell is responsible for Growth Factor Secretion?
Macrophages
115
What cell is responsible for Neovascularization?
endothelial cells
116
What cell is responsible for Collagen deposition?
fibroblasts and myofibroblasts
117
What cell is responsible for Collagen remodeling / retraction?
fibroblasts
118
What cell is responsible for Re-epithelialization / Regeneration?
epithelial cells cells and hepatocytes
119
What are labile tissues?
Continuous turnover from stem cells and proliferation of mature cells (e.g. bone marrow, surface epithelia such as skin, oral cavity, GI, ducts, urothelium, etc.)
120
What are stabile tissues?
minimal replicative activity, although capable of proliferating in response to injury or loss of tissue mass (e.g. parenchyma of most solid organs such as liver, kidney, pancreas; also endothelial cells, fibroblasts, smooth muscle cells); with exception of liver, stable tissues have limited capacity to regenerate after injury
121
What are permanent tissues?
Terminally differentiated and nonproliferative. Most neurons and cardiac muscle cells. Limited stem cell replication and differentiation, but insufficient for regeneration. Thus, repair dominated by scar formation.
122
What are two properties of stem cells?
Self-renewal
| Asymmetric replication
123
What is an embryonic stem cell?
most undifferentiated, present in inner cell mass of blastocyst can form all three germ cell layers: ectoderm, endoderm, mesoderm
124
What is an adult stem cell?
less undifferentiated than ES cells and found among differentiated cells within an organ or tissue. More limited self-renewal capacity, and more restricted lineage potential. Important in tissue homeostasis.
125
What is the basement membrane made up of?
**Type IV collagen
laminin
proteoglycans
126
What is the interstitial matrix comprised of?
Fibrillar collagens
elastins
proteoglycans and hyaluronan
127
What is the main function of the extracellular matrix?
Mechanical support
Control of cell proliferation
Scaffolding for tissue renewal
Establishment of tissue microenvironments
128
What happens if the extracellular matrix (ECM) is damaged?
repair can be accomplished only by scar formation
129
What is the most important cytokine for synthesis and deposition of connective tissue proteins?
transforming growth factor TGF-ß
130
What enzyme is responsible for the degradation of collagens and other ECM components? aka remodeling of connective tissue
**metalloproteinases (MMPs)
131
What is a hypertrophic scar?
accumulation of collagen outside boundaries of injury / regresses
132
What is a keloid scar?
accumulation of excessive amounts of collagen outside boundary of injury that persists
133
What is granulation tissue comprised of?
Comprised of fibroblasts, new capillaries (angiogenesis), loose extracellular matrix, and inflammatory cells (predominantly macrophages) (seen beneath scab of wound)
134
steps to form normal scar?
angiogenesis -> granulation tissue -> maturation and reorganization of fibrous tissue
(remodeling) -> stable fibrous scar
135
VEGF is used for what?
Vascular endothelial growth factor
angiogenesis!
136
How much of the liver can be removed in liver donor transplantation?
40-60%
137
What are the three Gf involved in Deposition of Connective Tissue?
PDGF (platelet derived growth factor) , FGF-2 (fibroblast growth factor), and TFG-ß (transforming growth factor)
138
what is a contracture scar?
Scar that crosses the joint line
139
What is healing by first intention?
epithelial regeneration is the principal mechanism of repair
140
What is healing by secondary intention?
combination of regeneration and scarring. You also get wound contracture due to myofirbroblast
141
Which drug has no anti-inflammatory element?
acetaminophen
142
Primary use of aspirin?
inhibition of platelet aggregation
143
When should you prescribe celecoxib?
When your patient needs anti-inflammatory action but cant put up with GI upset
144
action of endothelial cox II
makes anti sticky prostaglandins for platelets **antiaggretory
145
action of endothelial cox I
pro sticky postaglandins for platelet. **proaggregation
146
The cox I pathway in platelets makes..
makes thromboxane (TXA2)
147
The cox II pathway in endothelial cells makes..
makes prostacyclin (PGI2)
148
Why is the anti platelet effect of aspirin Cox 1 selective
1. pharmacodynamics - the endothelial cells have nucleus where as platelets do not. When endothelial cells are inhibited they can make more enzymes to counteract. A platelet needs to be made from scratch once it has been inhibited
2. Pharmacokinetics - acetylsalicyilic acid is presystemic in the hepatic portal vein and therefore interacts with platelets in the circulation more easily vs the tissue endothelial tissue cell COX II
149
What effect does cox I have on GI tract?
It's cytoprotective - decreasess acid / pepsin secretion and increases mucous / bicarbonate production
150
What effect does cox I have on smooth muscle?
increases contraction (think increased platelet aggregation)
151
What effect does cox I have on kidneys?
increases renal blood flow --> increased urine flow (diuresis)
152
which cyclogenase pathway is induced?
COX II
153
What effects does COX II have on uterine smooth muscle?
Contributes to labor contractions near parturition
154
What effect does COX II have on ductus arteriosus?
Maintenance of patent ductus arteriosus via vasodilation
155
What type of inhibition for tNSAIDS?
reversible inhibition COX I and COX II
156
What type of inhibition for celecoxib?
reversible selective inhibition of COX-2
157
What type of inhibition for acetaminophen?
reversible inhibition of Cox II in the **CNS no peripheral effect like anti inflammation
158
What type of inhibition for aspirin?
irreversible inhibition of COX-1 and COX-2. Because its irreversible its selective for COX I
extra anti-platelet effect! Not so much against fever and pain
159
What drug would you give for anti-platelet effect?
low dose aspirin
160
What drug for analgesic effect?
moderate doses NSAID COX II selective and aspirin
161
What drug dose for antipyretic effect?
moderate dose
162
What drug dose of anti-inflammatory effect?
High dose
163
What drug is a reversible inhibitor of COX I and II?
tNSAIDS: ibuprofen, naproxen
164
Which drug in large doses is metabolized to product toxic to liver?
Acetaminophen (tylenol)
165
COX II inhibitors reduce what symptoms?
pain, inflammation, fever, uterine contraction, ductus arteriosus dilation, renal dilation,
166
COX I inhibitors (nSAIDS, aspirin) reduce what symptoms?
platelet agglutination, GI protection, renal blood flow
167
Ketorolac
analgesic drug in IM/IV form
168
Ibuprofen
antipyretic and as effective as aspirin and acetaminophen
169
What drug should you give for anti-inflammatory response?
Efficacies similar - choice based on individual response or tolerance of side effects and half-lives or route
**Except acetaminophen which has no anti-inflammatory element
170
Safest over-the-counter pain medication to recommend to patients with gastric ulcers?
Acetaminophen
171
What side effect do tNSAIDS have on platelets?
increases bleeding! (COX I inhibitor)
172
Safest agent for pain treatment in patients taking oral anticoagulants?
Acetaminophen (tylenol)
celecoxib inhibits the antithrombosis component in endothelial COX II
173
Which NSAID if you are GI sensitive?
Ibprofen **inhibits COX II
174
Which NSAID if you are at risk of cardiovascular failure?
Naproxen **inhibits COX I more than COX II
175
NSAID alternatives for pain for elderly patients?
Acetaminophen, tramadol, and opioids
176
what is omeprazole?
proton pump inhibitor
177
Why does acetaminophen lack an anti-inflammatory effect?
Peroxide formation at sites of inflammation inhibits the activity of acetaminophen
178
Safest agent to treat musculoskeletal pain in patients with kidney dysfunction?
Acetaminophen
179
Relative to ibuprofen (Advil), agents that preferentially inhibit COX-2 over COX-1 will cause a higher incidence of
Clotting-related disorders
180
Aspirin is often used in low doses to prevent platelet aggregation by inhibiting the synthesis of which substance?
Thromboxane A2
181
A 16-year-old girl comes to the emergency department suffering from the effects of an aspirin overdose. Which of the following syndromes is this patent most likely to exhibit as a result of this drug overdose?
Hyperthermia, metabolic acidosis, and coma
182
What is the major endogenous glucocorticoid?
cortisol
183
What is the major exogenous glucocorticoid?
prednisone
184
What is the major endogenous mineralcorticoid?
aldosterone
185
What is the benefit of administering a glucocorticoid?
anti inflammatory
186
What is the effect of too much aldosterone?
retaining too much sodium and losing too much potassium
187
What is adrenal crisis?
Insufficient adrenal response to environmental stressors occuring due to chronic use of exogenous glucocorticoids
188
What are the glucocorticoid metabolic effects?
Carbohydrate: gluconeogenesis, blood glucose ( insulin) all increase
protein break down --> increased amino acids
fat break down --> free fatty acids
189
Metabolic effects of iatrogenic cushing's disease?
hyperglycemia, muscle wasting, centripetal obesity
insulin and cortisol compete. Cortisol wins in the periphery (fat breakdown) Insulin wins centrally (storage). Fat in the trunk! = centripetal obesity
190
What are signs of hypertension, sodium fluid retention, hypokalemia, and metabolic alkalosis?
Increased aldosterone
191
What is a key molecular component for functional cortisol?
You need a hydroxyl group at position 11
192
What is the benefit of using dexamethosone?
glucocorticoid that does not increase mineralcorticoid activity
193
What is the benefit of using fludrocortisone?
glucocoriticoid that increase mineralcorticoid activity
Useful if patient is **hyponatremic and dehydrated
194
Which organ activates cortisol?
the liver
195
Which organ inactivates cortisol?
kidneys
196
What is the primary clinical advantage of the alternate day glucocorticoid regimen?
Minimizes glucocorticoid block of ACTH release which can significantly reduce adrenal atrophy
**the anti-inflammatory result will withstand for 48 hours
197
Which corticosteroids need to go through the liver to be activated?
cortisone and prednisone
198
What is a key difference between prednisone and methylprednisolone?
Methylprednisolone you can administer topically!
199
Which drug is the most potent anti-inflammatory agent, used in cerebral edema, chemotherapy-induced vomiting; no mineralocorticoid action, greatest suppression of ACTH secretion at pituitary?
Dexamethasone
200
Which drug is a potent systemic agent - excellent topical activity; no mineralocorticoid action?
Triamcinolone
201
What are disease modifying antirheumatic drugs (DMARDs) used for?
added as soon as the diagnosis of rheumatic disease is certain with the aim of suppressing disease progression
202
When does thrombosis in the arterial system most commonly occur?
endothelial injury and turbulent blood flow, often associated with **atherosclerosis.
203
Where does arterial thrombi most commonly occur?
in the coronary, cerebral and femoral arteries.
204
What is an embolus?
A free floating, intravascular mass of a solid, liquid or gas
205
Where do Emboli in the venous/right sided system commonly lodge?
In the lungs
206
Where do Emboli in the arterial/left sided system commonly lodge?
any organ but most commonly the legs and brain
207
What is Disseminated intravascular coagulation (DIC)?
a unique condition where thrombosis and hemorrhage can occur simultaneously.
208
signs of acute onset of DIC
bleeding
209
signs of chronic onset of DIC
thrombosis
210
What are infarcts?
Infarcts are areas of tissue death (necrosis) caused by
| ischemia.
211
What is petechia?
small hemorrhage 1-2 mm
212
What is purpura
hemorrhage 3cm
213
What is echymoses?
bruise 1-2cm hemorrhage
214
Hematoma
large collection of blood in organ or tissue
215
What is the virchow triad that leads to thrombosis?
endothelial injury, hyper coagulability, abnormal blood flow
216
How do you tell if a thrombus is formed before death or post mortem?
lines of zohn indicate thrombus before death
217
What is a white infarction?
an arterial blockage, a single blood supply, and a dense tissue that limits accumulation of blood in necrotic areas.
218
What is a red infarction?
venous occlusion, a dual blood supply and loose tissue that permits movement of blood from adjacent areas into the necrotic area
219
Shock due to?
inadequate blood flow to tissue
220
Signs of shock?
coolness and pallor of their skin, tachycardia, and decreased urine output.
221
Signs of septic shock?
Fever, DIC, ARDS
Widespread
Arterial vasodilation --> hypotension, warm, flushed skin
Vascular leakage --> hypotension, edema
Venous blood pooling --> reduced cardiac output, increased heart rate
222
Define diapedesis
the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation.
223
Where are toll like receptors located?
On the plasma membrane or endosomes
224
What is the step by step roll of a toll like receptor?
The TLR is activated and then triggers the production of transcription factors to produce mediators of inflammation and anti-microbial products
225
What do inflammasomes recognize?
stuff from dead or damaged cells
226
What is the role of a leukocyte once it has been activated?
1. readily phagocytize materials
2. are poised to kill/degrade engulfed material
3. readily secrete material to kill/degrade
4. Produce inflammatory mediators (amplifies inflammatory process)
227
When do you expect to see a granulomatous infection?
In difficult to eradicate infections
228
Where are eosinophils predominantly found
allergies and parasitic infections
229
What blood measurement can you use to detect/monitor the presence of inflammation
serum amyloid A, c-reactive protein, and fibrinogen
230
neutrophilia is classic for what type of infection
bacterial infection.
231
What is meant by quiescent tissue/cells and give an example
normally little turnover but there is a capacity for proliferation.
example would be the liver
232
What is hypertrophy?
increase in cell size
233
What is hyperplasia?
increase in cell number
234
What is metaplasia?
Change from one benign, differentiated cell type to another, usually in response to injury (eg: inflammation)
235
Is neoplasia reversible or irreversible?
generally irreversible
236
What type of neoplasm is typically circumscribed/encapsulated?
benign neoplasm
237
adenoma originates from what type of tissue?
epithelial (benign)
238
osteoma, chondroma, and fibroma originate from what tissue type?
mesenchymal
239
sarcoma tissue origin?
mesenchymal
240
carcinoma tissue origin?
epithelial (malignant)
241
What type of cancer is the most common?
carcinomas (cancer of the epithelium)
242
What is dysplasia and why is it significant?
means disordered cell growth and is a hallmark of early premalignant neoplasia
243
Main difference between sarcoma and carcinoma?
sarcomas do not have a premalignant or in-situ phase
244
What is invasion?
the infiltration of adjacent tissues by malignant cells.
245
What is metastasis?
the transfer of malignant cells from the primary site to a non-connected (secondary) site.
**So metastases are tumors discontinuous with the primary tumor.
246
What is meant by an in-situ epithelial cancer?
In situ epithelial cancers display the cytologic features of malignancy without invasion of the basement membrane.
247
What are the methods of dissemination for cancer?
1. direct seeding of body cavities or surfaces
2. lymphatic spread
3. hematogenous spread
248
What are the steps in the metastatic cascade?
1. invasion - invasion through the basement membrane and ECM
2. intravasion- getting into the blood or lymph
3. extravasion - getting out of the blood or lymph
4. colonization
249
epithelial cells are held together by what proteins?
e-cadherins
250
How do tumor cells manipulate the system to dissociate one cell from another?
they down regulate the production of e-cadherins
251
What is the second stage of invasion for cancer cells?
local degredation of teh basement membrane and interstitial connective tissue by secretion of proteolytic enzymes or inducing stromal cells to make them
**Matrix-Metallo Proteases (MMP)
252
Describe what ameboid migration is
cancer cells squeeze through the spaces in the matrix instead of cutting through with proteases.
**quicker and why MMP inhibitors won't work on their own.
253
What is the 3rd stage of invasion in cancer cells?
changes in attachment of tumor cells to the extracellular matrix proteins to stimulate migration
254
What are some of the transcription factors that repress transcription of the e-cadherin gene?
SNAIL, TWIST, ZEB1/2
255
What does the repression of e-cadherin ultimately lead to?
epithelial to mesenchymal transition (EMT)
256
What is CARCINOMA-ASSOCIATED “PARANEOPLASTIC SYNDROME” ?
consequence of the presence of cancer, but not due to the local presence of the cancer cells. Thought to be due to hormones or cytokines excreted by tumor cells and/or immune response triggered by the tumor.
**indirect.
257
What is the most common route of metastasis for carcinomas?
Lymphatic spread
258
What is the most common route of metastasis for sarcomas?
hematogenous spread
259
What is the main cause of death due to cancer?
infection
260
What are some of the causes of mortality due to cancer?
1. infection
2. organ failure
3. hemorrhage
4. thromboembolism
5. emaciation
261
What are the 3 most common cancers among men?
1. Prostate (26%)
2. Lung (14%)
3. colon/rectal (14%)
262
What are the 3 most common cancers among women?
1. Breast (29%)
2. Lung (13%)
3. colon/rectal (8%)
263
What are the three leading types responsible for cancer mortality for men?
1. Lung (28%)
2. Prostate (9%)
3. colon/rectal (8%)
264
What are the three leading types responsible for cancer mortality for women?
1. Lung (26%)
2. Breast (15%)
3. colon/rectal (9%)
265
In order for a structure to be carcinogenic, what must happen?
must be activated by cytochrome p450
266
What is emphysema?
a condition in which the air sacs of the lungs are damaged and enlarged, causing breathlessness.
267
What are the four main groups of carcinogens?
polycyclic aromatic hydrocarbons
aromatic amines
nitrosamines and nitrosamides
aflatoxins
268
what does the ames test do?
Identifies mutagenic products
269
What is meant by "stage"
the extent of tumor spread at the time of diagnosis
270
What does TNM classification stand for?
T: size of tumor
N: lymph node involvement
M: presences of metastasis
271
What is meant by "grade"
refers to the state of differentiation of the tumor cells seen in histological sections.
272
What is low grade
means cells are well differentiated and exhibit features of normal cells
273
What is high grade?
The cells do not resemble normal epithelial cells
274
What are the pathologic features of squamous cell carcinoma?
in major branches of the bronchial tree "centrally"
squamous cells (instead of ciliated columnar epithelial)
necrosis and hemorrahgic
well differentiated
positive for keratin **keratin pearls
275
What are the pathologic features of adenocarcinoma?
centrally or in the periphery of the lung
forms primitive gland like structures
**stains positive for mucin
276
What are the pathologic features of large cell carcinoma?
undifferentiated
high grade lung cancer
may not produce either keratin or mucin
277
What are the pathologic features of small cell carcinoma?
```
can happen anywhere in the lung
high grade cancer
cells are small and dark staining
cells form clusters
stains positive for neuroendocrine markers
```
278
Which cancers are strongly linked to cigarette smoking?
squamous cell carcinoma
| small cell carcinoma
279
What are risk factors for pancreatic cancer?
age, smoking, chronic pancratitis from alcoholism, diabetes mellitus, family history
280
What is the prognosis for pancreatic and lung cancer?
low/poor (pancreatic cancer even worse)
281
What are the pathologic features of pancreatic cancer?
well differentiated adenocarcinoma
primitive gland like structures
mucin production
282
What is desmoplasia and what cancer is it associated with?
a prominent connective tissue stroma
**the reason why pancreatic cancers feel rock hard
283
What are risk factors for lung cancer?
smoking, age, occupational history (mining, exposure to metal vapors, etc), exposure to air pollutants, and family history.
284
What are the three inherited conditions that increase risk of colorectal cancer?
1. rare familial adenomatous polyposis (APC)
2. Rare loss of mismatch DNA repair (HNPCC)
3. mutY base excision DNA repair enzyme
285
What are the pathologic features of colorectal cancer?
well differentiated adeocarcinoma
| innermost, mucosal layer of bowel wall
286
What is the Gleason system?
A grading system for prostate cancer. The Gleason grade of the predominant pattern and the Gleason grade of the subordinate pattern are added together.
Values of 8 to 10 indicate aggressive behavior → can kill Pt
287
What type of lung cancer is not treating with surgery?
small cell carcinoma
288
Which cancer is associated with EGFR mutations?
adenocarcinomas
289
What cancer do these drugs treat? Gefitinib, erlotinib, afatinib, critzotinib
Adenocarcinoma
290
Describe the nuclear changes that occur during the breakdown of DNA and chromatin
Pyknosis - nuclear shrinkage/ condenses
Karyorrhexis - nucelar fragments
Karyolysis - dissolution of nucleus
291
What is coagulative necrosis?
tissue architecture preserved due to damage to structural proteins and enzymes
-appear as pale "ghost cells"
292
When does coagulative necrosis typically occur?
myocardial infarcts
| any organ after an infarct
293
What is liquefactive necrosis?
Dead cell dissolves - lysosomal hydrolases digest cell compartments
294
When does liquefactive necrosis typically occur?
bacterial / fungal infections
| also CNS following hypoxic conditions
295
What is Caseous necrosis?
a collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border
296
When do you see caseous necrosis?
tuberculosis
297
What is fat necrosis?
Necrotic adipose tissue - fats are hydrolyzed into free fatty acids → ppt with Ca2+ →chalky gray material
298
When do you see fat necrosis?
acute pancreatitis or trauma
299
What is fibrinoid necrosis?
immune reaction in which complexes of antiges and antibodies are deposited in the walls of arteries
300
When do you see fibrinoid necrosis?
vasculitis
| polyarteritis nodosa
