D&D Unit 1-2 Flashcards
(230 cards)
1
Q
Human disease occurs mostly from injury to the _________
A
Epithelium
2
Q
What is metaplasia?
A
A reversible change in which one adult cell type is replaced by another cel type
3
Q
5 types of necrosis
A
Coagulative Liquefactive Caseous Fat Fibrinoid
4
Q
What is coagulative necrosis?
A
Tissue architecture is preserved for at least several days before they are digested
5
Q
What is liquefactive necrosis?
A
Usually in infections where leukocyte enzyme digest tissue Also forms in hypoxic death of CNS cells
6
Q
What is caseous necrosis?
A
Looks chalky white- like casein (milk) Central portion of an infection is necrotic (fragmented or lysed cells) and inflamed on borders
7
Q
When does fat necrosis occur?
A
From release of pancreatic lipases Or from trauma to fat areas
8
Q
4 reversible changes that occur in hypoxia
A
Decreased ATP
Decrease Na pump -> swelling
Increased glycolysis -> decreased pH
Decreased protein synthesis
9
Q
3 irreversible changes that occur in hypoxia
A
Activation of lysosomal enzymes
DNA and protein degradation
Ca2+ influx
10
Q
4 big picture cellular adaptations to stress
A
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
11
Q
Metaplasia nomenclature
A
Metaplasia is named for whatever tissue replaces normal tissue
12
Q
Why does fat accumulate in injured cells as lipid vacuoles in the cytoplasm?
A
Increased entry and synthesis of free fatty acids Decreased fatty acid oxidation
13
Q
4 intracellular changes associated with reversible cell injury
A
Plasma membrane alterations (blebbing, blunting, distortion, loosening of intercellular attachments)
Mitochondrial changes (swelling and appearance of phospholipid-rich amorphous densities)
Dilation of ER with detachment of ribosomes and dissociation of polyribosomes
Nuclear alterations with chromatin clumping
14
Q
Describe pyknosis
A
Nuclear shrinkage and increased basophilia (chromatin condenses) Step 1
15
Q
Describe karyorrhexis
A
The pyknotic nucleus fragments Step 2
16
Q
Describe karyolysis
A
The nucleus dissolves Step 3
17
Q
What type of necrosis is gangrene?
A
A coagulative necrosis involving multiple tissue layers
18
Q
What is fibrinoid necrosis?
A
An immune reaction in which complexes of antigens and antibodies are deposited in walls of arteries and combine with fibrin
19
Q
How does ischemia cause mitochondrial damage and dysfunction?
A
Failure of oxidative phosphorylation causes:
ATP depletion
Formation of ROS
Formation of pores and loss of membrane potential
Release of proteins that activate apoptosis
20
Q
Changes to intracelluar calcium in cellular damage
A
Release of calcium stores from inside
Increased influx accross plasma membrane
21
Q
2 ways reactive oxygen species accumulate in cellular damage
A
Mitochondria
Phagocytes
22
Q
3 important sites of cellular membrane damage
A
Mitochondria
Plasma membrane
Lysosome
23
Q
The intrinsic apoptotic pathway is mediated by ________
A
Mitochondria
24
Q
The extrinsic apoptotic pathway is mediated by ________
A
Death receptor
25
4 ways cells can accumulate shit
Inadequate removal
Accumulation of abnormal endogenous substance
Failure to degrade (storage diseases, usually genetic)
Deposition and accumulation of abnormal exogenous substance
26
What is steatosis?
Fat within cells
27
The inflammasome stimulates inflammation via activation of \_\_\_\_\_\_\_\_\_\_
Caspase-1
28
In the inflammasome, caspase-1 activates \_\_\_\_\_\_\_\_\_\_
IL-1 Beta
29
3 reasons why permeability occurs in inflammation
Endothelial cell contraction
Endothelial injury (they die or detach)
Transcytosis
30
Short-term vascular permeability is mediated by __________ and __________ while longer-term permeability is mediated by __________ and \_\_\_\_\_\_\_\_\_\_
Histamine
Bradykinin
(1 hr)
?
31
What is margination?
In initial phase of leukocyte recruitment, leukocytes accumulate on vascular endothelium so they move to the side of the laminar flow
32
Leukocytes stop rolling when __________ are engaged
Integrins
33
What is leukocyte transmigration
Pushing between endothelial cells
Usually occurs in venules
34
4 things macrophages produce via classical activation to fuck shit up
Reactive oxygen species
Nitrous oxide
Lysozymal enzymes
Proinflammatory cytokines
35
3 things that cause classical activation of macrophages
Endotoxin
IFN-gamma
Foreign material
36
What do alternatively activated macrophages do?
Produce growth factors for new vessel growth and fibroblast activation for tissue repair and fibrosis
37
What types of immune cells are hallmarkers of acute inflammation?
Neutrophils
38
3 places pro-inflammatory receptors can be on
Plasma membrane - extracellular triggers
Endosomes - ingested triggers
Cytosol - intracellular triggers
39
What does the inflammasome respond to?
Stuff from dead or damaged cells
(It is inside the cell)
40
Whta is the difference between exudate and transudate?
Exudate is a result of increased vascular permeability from inflammation
Transudate is a result of altered intravascular pressure from hemodynamic or osmotic changes
41
How is the phagocytotic target bound? (2 receptors)
Receptors for specific products of microbes or necrotic cells
Receptors for opsonins
42
How are ROS formed and what do they do? Like the process
ROS formed by oxidation of NDAPH which converts oxygen to a superoxide ion
Superoxide ion converts to H2O2
H2O2 converted to hypochlorous radical
43
How long to monocytes circulate for before they become macrophages in tissue?
About a day
44
3 roles of macrophages
Ingest stuff Initiate tissue repair Secrete inflammatory mediators like cytokines and eicosanoids that promote inflammation
45
Mast cells release __________ and __________ inflammatory mediators
Histamine Arachadonic acid
46
What is a granuloma?
Enlarged macrophages that form a nodule
Often surrounded by lymphocytes
Fibrosis often forms around longastnding granulomatous inflammation
47
3 chemical mediators responsible for many of the systemic effects of inflammation
TNF IL1 IL6
48
What about inflammation causes production of C-reactive protein and serum amyloid A? Where does this occur?
IL-6 induces hepatcytes to produce
49
What 2 chemicals cause the bone marrow to release more leukocytes in inflammation?
TNF
IL1
50
4 cell types that make arachidonic acid
Lekocytes
Mast cells
Endothelium
Platelets
51
What are lipoxins?
Are generated as leukocytes enter tissues Antagonize lekotrienes and are anti-inflammatory Inhibit neutrophil chemotaxis and endothelial adhesion
52
5 things platelet-activating factor does
Platelet aggregation
Vasodilation
Vascular permeability
Bronchoconstriction
Stimulation of platelets and other cells to make mediators
53
Production of platelet-activating factor
Phospholipase A2 cleaves lipids form cell membranes
54
What do chemokines do? (2)
Chemotaxis
Activate leukocytes
55
Production of NO
Made by nitric oxide synthase from L-arginine
56
What is the difference between type II and type III nitric oxide synthase
Type II is induced in macrophages and endothelial cells in inflammation
Type III is constitutively expressed in endothelial cells
57
What is substance P secreted by? What does it do?
Secreted by nerves and inflammatory cells
Binds the neurokinin-1 receptor
Generates proinflammatory effects in immune and epithelial cells
58
What does C3 convertase do in complement?
Cleaves C3 into C3a and C3b
59
What are 3 inhibitors of compliment?
C1 inhibitor blocks activation of C1
Decay-accelerating factor (DAF) and factor H limits C3/C5 convertase formation
60
What does Factor XII/hageman factor do?
Activates the kinin system
Stimulates the clotting cascade
61
What does IL-10 do? What makes it?
Downregulates activated macrophages
Secreted by macrophages
62
What are the cells responsible for the following components of repair?
1. Growth factor secretion
2. Neovascularizaiton
3. Collagen deposition
4. Collagen remodeling/retraction
5. Re-epithelization/regeneration
1. Macrophage
2. Endothelial cell
3. FIbroblast
4. Fibroblast
5. Epithelial cells/hepatocytes
63
What is granulation tissue and what is it made of?
New tissue
Is pink and has a soft granular appearance
Made of fibroblasts, new capillaries, loose ECM, and inflammatory cells (mostly macrophages)
64
What is the difference between hydrostatic and oncotic pressure?
Hydrostatic pressure pushes fluid out into the interstitial space on the arterial end
Oncotic pressure pulls fluid back in to balance protein concentration on the venous end
65
How does the Virchow triad contribute to thrombosis?
Endothelial injury
Abnormal blood flow (stasis or turbulence)
Hypercoaguability
66
What are the 3 types of adrenal corticosteroids?
Glucocortigoids (cortisol)
Mineralocorticoids (aldosterone)
Adrenal androgens (DHEA, androstenedione)
67
ACTH is made by the \_\_\_\_\_\_\_\_\_
Pituitary
68
ACTH release is controlled by \_\_\_\_\_\_\_\_\_
corticotropin-releasing factor
69
Corticotropin-releasing factor is made by the \_\_\_\_\_\_\_\_\_
Hypothalamus
70
3 modes of regulation by the hypothalamic-pituitary-adrenal axis
1. Diurnal rhythm of basal steroidogenesis
2. Negative feedback by circulating corticosteroids
3. Stress can override negative feedback and increase steroidogenesis
71
What are 3 drugs that decrease glucocorticoid production?
Metyrapone
Mitotane
Trilosane
72
What is the rate-limiting step in the glucocorticoid pathway? What is it stimulated by?
Conversion of cholesterol to pregnenolone
ACTH stimulates
The RAA system via angiotensin II also stimulates via the mineralocorticoid pathway
73
When are natural cortisol peaks in circadian rhythm?
Early morning
After meals
74
Is plasma-bound cortisol active?
No. Only free cortisol is active.
75
How is cortisol metabolised?
Reduced in liver
Conjugated in liver
Eliminated in uring
76
What are the effects of glucocorticoids on:
Carbohydrates
Protein
Lipids
Net effect
*Carbs:* Stimulates gluconeogenesis, increasing blood glucose.
Stimulation of glycogen synthase activity increases liver glycogen deposition
* Proteins*: increased amino acid uptake into liver and kidney and decreased protein synthesis (except liver) leads to a transfer of amino acids from muscle and bone into liver
* Lipids:* Inhibition of uptake of glucose by fat cells stimulates lipolysis. However, there is also insulin resistance leading to lipogenesis, especially in trunk -\> central obesity
The net result is maintainin the glucose supply to the brain
77
What are permissive effects and what are 2 that happen wih glucocorticoids?
Permissie effects are responses that occur to an appreciable extent only in the presence of glucocorticoids, but don't increase with increasing amounts of glucocorticoids
1. Vasoconstrictuion and bronchodilation response to catecholamines
2. Fat cell lipolysis response to catecholamines, ACTH, growth hormone
78
What happens when aldosterone binds to its receptor?
Cytosolic receptor migrates to the nucleus where it induces synthesis of membrane channels (Na/K ATPase, Na, K)
This increases reabsorption of Na+ from distal renal tubules that is coupled to increased secretion of H+ and K+
79
What are glucocorticoids used for pharmacologically?
To suppress inflammatory and immune responses
80
Glucocorticoid administration decreases synthesis of \_\_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_, and __________ inflammatory and immune mediators
Cytokines
Leukotrienes
Prostaglandins
81
How do glucocorticoids reduce generation of leukotrienes and prostaglandins.
Decreases expression of COX-2 in inflammatory cells (decreased prostaglandins only)
Inhibits phospholipase A2 via lipocortin
82
How do glucocorticoids suppress the immune system? (3)
Suppress T cell activation
Supress cytokine production
Prevent eosinophils from releasing things
83
What effects do glucocorticoids have on lymphoid areas?
Decrease clonal expansion of T and B cells
Decrease cytokine production, but this has little effect on antibody formation at moderate doses
84
What effects do glucocorticoids have on the vasculature?
Reduce vasodilation
Decrease fluid exudation
85
What effects do glucocorticoids have on areas of acute inflammation?
Decrease number and activity of leukocytes by causing them to move to lymphoid tissues
Neutrophils move into circulation and out of peripheral tissues
86
What effects do neutrophils have on chronic inflammation?
Decreased activity of monocyte and lymphocytes
Decreased proliferation of blood vessels
Less fibrosis
87
What is a mineralocorticoid?
An agent that causes Na+ retention at the kidney
88
Are 11-hydroxy glucocorticoids physiologically active?
Are 11-keto glutocorticoids?
Yes
No. They are prodrugs that must be activated by 11beta-hydroxysteroid dehydrogenase (11B-HSD1)
89
What does the liver do to glycocorticoid drugs?
11beta-HSD1 converts cortisone to cortisol
Activating step
90
What does the kidney do to glucocorticoid drugs?
11Beta-HSD2 converts cortisol to cortisone
Inactivating step
91
What hormone actions does cortisol have as a drug?
How is it administered?
Glucocorgicoid and mineralcorticoid (1:1 ratio)
Oral and parenteral administration
92
What hormone actions does prednisone have?
Glucocorticoid and mineralcorticoid actions (13:1)
Activated to prednisolone in liver - must go through first pass metabolism
93
What hormone actions does dexamethosone (decadron) have?
No mineralocorticoid action, all glucocorticoid
94
What hormone actions does methylprednisolone have?
Minimal mineralocorticoid action - mostly glucocorticoid
95
What hormone actions does triamcinolone have?
No mineralocorticoid action - all glucocorticoid
96
5 toxicities of systemic steroid drugs with high dose sustained therapy
In addition to acute effects,
Iatrogenic Cushing's syndrome (hyperglycemia, muscle wasting, lipid deposition)
Hypothalamic-pituitary-adrenal axis suppression -\> insufficient response to stress
Mood disturbance (initial euphoria, then letdown when reduced)
Impaired wound healing
Increased susceptibility to infection
97
2 acute toxicities of systemic steroid drugs with short course therapy
Mineralocorticoid effects: Na+ and H2O retention -\> edema -\> increased BP, hypokalemia
Glucocorticoid effects: glucose intolerance, mood changes (up or down), insomnia, GI upset
98
4 toxicities of systemic steroid drugs with large cumulative doses
Osteoporosis
Cataracts
Skin atrophy, loss of collagen support
Growth retardation in children
Peptic ulceration
99
NSAIDS inhibit ___________ and \_\_\_\_\_\_\_\_\_\_\_
Cyclooxegenase 1 and 2 (COX-1 and COX-2), which produce inflammatory prostaglandins and thromboxanes
100
5 side effects of NSAIDS
GI: ulceration, bleeding, nausea
Bleeding problems
Renal: acute renal failure, interstitial nephritis
Uterine: interferes with contractions
Thrombosis: myocardial infarction, strokes
101
What do traditionsl NSAIDS do chemically?
Reversible inhibition of COX-1 and COX-2
102
What does acetophinophen do chemically?
Inhibits COX-2 onl in the CNS
103
What does aspirin do chemically?
Irreversible inhibition of COX-1 and COX-2
104
Contraindication for traditional NSAIDS
People at risk for peptic ulcer disease
- old
- history of PUD or prior NSAID gastropathy
Concurrent glucocorticoid anti-inflammatory use
105
What do traditional NSAIDS do the GI tract (side effect)
Interfere with gastric cytoprotection by inhibiting COX-1 PGE synthesis -\> dyspepsia and gastric ulceration
106
What do traditional NSAIDS do to platelets (side effects)?
Interfere with platelet aggregation by inhibiting COX-1 thromboxane A2 synthesis -\> more bleeding
107
What do traditional NSAIDS do to the kidneys?
Renal vasoconstriction by inhibition of COX-1 and COX-2 PGE synthesis and loss of vasodilator actions -\> reversible renal insufficiency
Fluid retention
108
What does celebrex/coloxib do chemically?
COX-2 selective inhibitor
109
What side effects does Celebrex/coloxib have on the GI tract with different dosing levels?
Less GI toxicitiy at low doses
High doses yes
110
Celebrex/coloxib effects on platelets
No increase in bleeding risk (no inhibition of COX-1 mediated TXA2 synthesis in platelets)
Increases risk of ischemic cardiovascular disease/heart failure
111
What 4 patient populations do you avoid celebrex/coloxib use in?
Can cause acute renal railure in:
Chronic renal insufficiency
Severe heart disease
Volume depletion
Hepatic failure
112
What are aspirin's effects on:
Pain
Inflammation
Fever
Platelets
Reduces inflammatory pain, but not so much pain that is from direct stimulation of sensory nerves
Antiinflammatory
Reduces elevated (but not normal) body temperature
Inhibits platelet aggregation
113
What is neoplasia?
Autonomous and progressive cell growth
114
What does TXA2 (thromboxane 2) do?
Causes platelet aggregation
115
What does COX-1 do to the GI tract, platelets, and kidneys?
GI: decreases acid/pepsin secretion, increases mucus/bicarb production
Platelets: pro-aggregatory
Kidneys: increases renal blood flow, promoting diuresis (a good thing)
116
What does COX-2 do in endothelial cells, the uterus, ductus arteriosus, tissue damage, and the hypothalamus?
ECs: vasodilation, anti-aggregatory platelet effects
Uterus: labor contractions
Ductus arteriosus: maintains it open
Tissue damage: pain/inflammation through vasodilation, potentiation of bradykinin pain-producing activity
Hypothalamus: fever
117
What is the chemical precursor of COX-1 and COX-2?
Arachadonic acid
118
What does inhibiting CNS COX-2 do?
What does inhibiting peripheral COX-2 do?
Reduce pain
Reduce inflammation
119
Where and what COX do you inhibit for analgesia?
What dosing level?
COX-2 at the site of tissue injury
Intermediate dosing
120
Where and what COX do you inhibit for antipyritic effects? What dosing level?
COX-2 in hypothalamus
Intermediate dose
121
Where and what COX do you inhibit for anti-inflammatory effects? What dosing?
COX-2 at sites of tissue njury
High doses, scheduling based on half-life
122
Where and what COX do you inhibit for antithrombic uses? What dosing?
COX-1 in platelets
Low doses (daily)
123
3 side effects of COX-1 inhibition
Gi ulceration, bleeding
Increased bleeding risk
Renal dysfunction
124
3 side effects of COX-2 inhibition
Renal dysfunction
Delayed labor
Increased thrombotic events
125
3 groups of patients at high risk for peptic ulcer disease
Being old
History of PUD or prior NSAID gastropathy
Concurrent glucocorticoid anti-inflammatory use
126
What drug do you give people with NSAIDS to reduce GI side effects?
Proton pump inhibitors
Omeprazole
127
How long is a platelet lifespan?
4-7 days
128
Why should you be concerned about using traditional NSAIDS with cardiovascular disease?
They cause fluid retention,
May exacerbate heart failure
May raise blood pressure
May interfere wth cardioprotective effect of aspirin
129
Which traditional NSAIDS have lowest and highest risk of GI problems?
Lowest- ibuprofen
Highest - naproxen
130
Which traditional NSAIDS have lowest and highest risk of cardiovascular problems?
Lowest - naproxen
Highest - ibuprofen, celecoxib
131
Greater COX-1 inhibition results in increased __________ system risk
Greater COX-2 inhibition results in increased __________ system risk
GI
CV
132
When is aspirin COX-1 selective (as opposed to COX-2)
Low doses
133
What are the 2 steps of aspirin metabolism?
Hydrolyzed by esterases
Conjugated with glycine or glucuronide
134
What are hydrostatic and oncotic/osmotic pressures?
Hydrostatic pressure pushes blood out of arteries. Due to fluid pressure.
Osmotic pressure pulls blood into veins. Due to albumin.
135
What is the difference between transudate and exudate?
Transudate is due to pressure differences
Exudate is due to increased vascular permeability (due to inflammation or endothelial damage)
136
How do the protein, LDH, and glucose fluid/serum ratios differ etween transudate and exudate?
What about specific gravity and white blood cell count?
Exudate is has more protein, LDH
but less glucose
Specific gravity is increased in exudate
WBCs are increased in exudate
137
What is hyperemia?
Physiologic/active increase in blood volume
Due to arteriolar dilation
Increase in oxygenated blood to tissue
138
What is vascular congestion?
Pathologic/passive increase in blood volume
Impaired venous outflow
Increased deoxygenated blood
139
How does conjestive heart failure work? (L heart failure)
Fluid buildup in lungs and pleural effusions
Low blood pressure (from cardiac insufficiency) -\> kidney tries to retain fluid and sodium -\> blood volume increases and blood dilutes -\> peripheral edema
140
What happens in liver congestion?
Portal backup -\> splenic congestion, GI tract varices (dilated veins in the GI tract), pleural effusion, pericardial effusion, ascites
141
What is a hematoma?
A hemmorhage within tissue
142
What are the 3 sizes of small hemorrhages?
Petechiae (1-2 mm)
Purpura (\>3 mm)
Ecchymoses (1-2 cm)
143
What is disseminated intravascular coagulation?
Thrombosis and hemorrhage occur at the same time
Systemic activation of coagulation causes widespread fibrin depositon and consumption of platelets and clotting factors
144
What is the difference between white and red (4 ways) infarcts?
White infarcts are in dense tissue where an artery is blocked off so there is no blood flow.
Red infacts are a venous blockage, when you restore blood flow after a tissue has died, loose tissue where blood can come form other places, or in organs that have dual blood flow like the lung
145
What are 3 kinds of shocks?
Cardiogenic - due to inability to pump blood
Hypovolemic - low blood volume
Septic
146
Glucocorticoids block the actions of ______________ and \_\_\_\_\_\_\_\_\_\_\_\_\_\_
Prostaglandins
Leukotrienes
147
Why can't cortisone be given topically?
It is not active until first pass metabolism
148
Glucocorticoid effects on carbs, protein, fat
Carbs: gluconeogenesis increases bloood glucose
Protein: decreased protein synthesis icreases synthesis of amino acids to glucose
Fat: lipolysis increases free fatty acids
149
What does excess glucocorticoid do to carbs, protein, and fat?
Carbs: diabetes-like state
Protein: muscle wasting, skin-connective tissue atrophy
Fat: central lipogenesis (via insulin) leading to central obesity
We get iatrogenic cushing's disease
150
What do mineralocorticoids do?
Increase sodium absorption
-\> increased blood volume and blood pressure
151
What happens with excess mineralocorticoid(4)?
Sodium-fluid retention, hypertension, hypokalemia, metabolic alkalosis
152
Glucocorticoid effects on vasculature, immune/inflammatory cells, immune/inflammatory mediators
Reduced vasodilation, decreased fluid exudation
Decrease in accumulation and activation of immune/inflammatory cells
Decrease in immune/inflammatory mediator synthesis
153
How does glucocorticoid metabolism work with fetuses?
Placental 11beta-HSD2 is active, but fetal liver 11beta-HSD1 is not
so, we can treat the mother with glucocorticoids without effects on the fetus since the drug wil be inactivated by 11beta-HSD2 and not activated by 11beta-HSD1
To treat a fetus with GCs, we use agents that are poor substrates for 11beta-HSD2
154
What is the primary clinical advantage of using the alternate day glucocorticoid regimen?
It minimizes the glucocorticoid block of ACTH relesae, which can significantly reduce adrenal atrophy
155
What cell type characterizes granulomatous inflammation?
Epithelioid histiocytes
156
4 steps of the metastatic cascade
1. Dissociation of cells from one another
2. Local degradation of the basement membrane and interstitial connective tissue
3. Changes in attachment of tumor cells to ECM proteins. Lose adhesion, modify matrix
4. Locomotion
157
What protein holds epithelial cells together?
E-cadherin?
158
Intracellularly, E-cadherins are connected to ___________ and \_\_\_\_\_\_\_\_\_\_\_
Beta-catenin
Actin cytoskeleton
159
2 types of tumor cell movement
1. Secretion of proteolytic enzymes, or induction of stromal cells to produce them
2. Ameboid migration - cell squeezes through spaces in matrix
Cancer cells often can switch between these
160
What is tumor stage? Why is it important?
REfers to the extent of tumor spread at time of diagnosis.
For many types of carcinoma, stage is the best predictor of prognosis
161
What are epithelial malignant neoplasms called?
Mesynchymal ones?
Hematopoietic ones (2 kinds)
Carcinoma
Sarcoma
Lymphoma
Leukemia
162
3 characteristic histological features of dysplasia
Loss of cytologic uniformity
Loss of normal histologic maturation
Loss of architectural orientation
163
What is histologic grade?
The degree of tumor histologic differentiation - like how much it resembles its normal tissue counterpart
Low grade - more differentiation/greater resemblance to normal
High grade - dedifferentiation/less resemblance to normal
164
What are the 6 things that cause disease?
Trauma
Toxicity
Tumor
Infection
Inflammation
Idiopathic
165
What is TNM tumor classification?
T - size of tumor (1-4)
N - lymph node involvement (number of lymph nodes)
M - metastasis (yes or no)
166
Is small cell lung cancer treated surgically?
No. Only by chemotherapy.
167
4 types of lung cancer
Squamous cell carcinoma
Adenocarcinoma (includes bronchioalveolar carcinoma)
Large cell carcinoma
Small cell (oat cell) carcinoma
168
5 subtypes of lung adenocarcinoma
Acinar predominant
Papillary predominant
Micropapillary predominant
Solid predominant
Invasive mucinous
169
What part of the pancreas does pancreatic carcinoma usually arise in?
Major ducts, not acini
170
What is the most common mutation in pancreatic carcinoma?
K-ras
171
What is the main cytologic feature of epithelial carcinoma in situ
Malignant without invasion of the basement membrane
This can be considered one step removed from invasive cancer
172
What is the correlation between primary tumor size and risk of developing metastasis?
They are strongly positively correlated
173
Epithelial cells are held together by \_\_\_\_\_\_\_\_\_\_\_\_\_
On the intracellular side, this is connected to _____________ and \_\_\_\_\_\_\_\_\_\_\_\_\_
E-cadherin
Beta-catenin
Actin cytoskeleton
174
What are 2 ways matrix metallo-proteases regulate tumor invasion?
1. Remodeling insoluble ocmponents o the basement membrane
2. Releasing ECM-sequestered growth factors that cleave ECM components and promote cell growth
175
What is paraneoplastic syndrome?
Hormones and cytokines excreted by tumor cells and/or immune response triggered by the tumor
-\>
Weird systemic effects
176
What are 2 things carcinogenesis requires? (in terms of carcinogens)
Time (several years elapse after exposure to the carcinogen before cancer emerges)
Cell proliferation
177
What cell type is at risk for becoming malignant?
The stem cell
Fully differentiated cells never become malinant
178
What are cancer promoters?
Irritants that cause inflammation and cell proliferation
179
What does kallikrein do?
Convertes high molecular weight kinin (HMWK) to bradykinin
180
How do selectins work?
Selectins are on endothelial cells and interact with glycoprotein ligands on neutrophils. This is important during the rolling stage of neutrophil recruitment
181
What are lipoxins derived from?
Arachadonic acid
182
Is lipoxin pro or anti-inflammatory?
Anti-inflammatory
183
Prostaglandins, leukotrienes, thromboxanes, and lipoxins are subfamilies of \_\_\_\_\_\_\_\_\_\_\_\_
Eicosanoids
184
Where do steroids act in the arachidonic acid metabolite pathway?
Steroids inhibit phopholipase. This prevents cell membrane phospholipids from becoming arachidonic acid, thus stopping production of many downstream meadiatiors of inflammation
185
What are the adhesion molecules on endothelial cells that mediate the processes of margination and rolling in inflammation? What do they bind to on leukocytes?
E- and P- selectin on endothelial cells bind to sugars on the surface of leukocytes
186
Where is bradykinin synthesized? Where is it activated?
Liver
Site of inflammation
187
What is coughing up blood called?
Hemoptysis
188
What secretes IL-12?
What does it do?
B cells secrete
Induces differentiation of T0 cells into Th1 cells
Activates NK cells
189
What do catalase and glutathione peroxidase do?
Eliminate free radicals
190
What are the 3 types of cancer chemotherapy?
Primary induction (drug treatment is the primary strategy)
Neoadjuvant (drug and then surgery/radiation)
Adjuvant (surgery/radiation and then drug)
191
How does BH3 profiling work?
Mitochondria are exposed to titrated doses of BH3 and mitochondrial outer membrane permeabilization is measured.
Less BH3 is needed in cells that are closer to apoptosis.
Linked to clinical response to chemotherapy drugs
192
BH3 is part of the ___________ protein
BCL, in the apoptosis pathway
193
4 common mechanisms of chemoresistance
Drug inactivation
Alterations to drug target
Adaptive responses to the drug effect (often increased repair of cellular damage)
Dysfunctional apoptosis (cell doesn't die when it should)
194
How do alkylating agents work as chemotherapy agents?
Form covalent bonds and crosslink DNA
Prevents DNA replication
DNA damage activates apoptosis
195
How do antimetabolites work as chemotherapy agents? What is the main example?
Intracellularly activated
Inhibits thymidylate synthase -\> dTTP depletion -\> inhibits DNA synthesis
INhibits DNA synthesis and activates apoptotic response because of DNA damage
5-Fluorouracil
196
How do topoisomerase chemotherapeutic agents work?
Something about DS breaks
DNA damage -\> apoptosis
197
What category of chemotherapeutic agents causes cardiotoxicity? Why?
Anthracyclins
Reduced chelating ability -\> radical damage (chelators and anti-oxidant enzymes are lower in cardiac tissue)
198
How do Vinca alkaloids work as chemotherapeutic agents?
Anti-microtubule
Bind to tubulin and cause depolymerization
199
How do taxanes work as chemotherapeutic agents?
Anti-microtubule
Stabilize against microtuble depolymerization -\> blocks mitosis -\> apoptosis
200
What 3 substances cause vasodilation?
Prostaglandins
Nitric oxide
Histamine
201
What 8 things cause increased vascular permeability?
Histamine
Serotonin
C3a
C5a
Bradyknin
Leukotrienes
Platelet-acivating factor
Substance P
202
What 2 complement components cause chemotaxis of leukocyes?
C3a
C5a
203
What 2 inflammatory substances cause pain?
Prostaglandins
Bradykinin
204
What 3 inflammatory mediators cause fever?
IL-1
TNF
Prostaglandins
205
Which cyclooxygenase inhibition is associated with each following symptom:
GI upset
Bleeding
Decreased renal function
Decrased uterine contraction
Increased clotting
1
1
1 & 2
2
2
206
What is ulceration?
Where epithelium is missing
207
What cell category lines the mesenteric surface?
Mesothelial cells
208
What enzyme levels do we measure for pancreatitis?
Lipase is elevated in pancreatitis
209
What hormone synthesize by the small bowel stimulates contraction of the gallbladder?
Cholecystokinin
210
What is hematemesis?
4 possible sources
Vomiting blood
Oral lesion
Esophageal lesion
Stomach lesion
Blood from a lung lesion being swallowed
211
What causes nutmeg liver?
Liver congestion
212
What strucure do aenocarcinomas form?
Glands
213
What cell type is small cell carcinoma (lung) derived from?
Neuroendocrine
214
What is a uterine smooth muscle tumor called?
Leiomyoma (benign)
Leiomyosarcoma (malignant)
215
What is a skeletal muscle tumor called?
Rhabdomyoma (benign)
Rhabdomyosacroma (malignant)
216
What is an endothelial cell tumor called?
Hemangioma (benign)
Angiosarcoma (malignant)
217
What are teh ABCDEs of moles?
Asymmetry
Border irregularity/bleeding
Color variation
Diameter
Evolution or elevation
218
What is the difference between the light and dark zone of the germinal center?
Light zone is more mature cells
Dark zone is increased mitotic activity
219
What is rituximab?
Anti CD20 antibody
220
What are 2 ways cellular injury occurs in hypoxia?
ATP reduction
Production of free radicals following reperfusion
221
What is an effusion?
Fluid accumulation in a body cavity
222
What is dysplasia?
Disordered cell growth
223
4 ways E-cadherin expression can be lost
Loss of heterozygosity
Inactivating mutation (rare)
Silencing of gene expression via hypermethylation of promoter
Transcriptional repressors like SNAIL, SLUG, TWIST\< ZEB1/2
224
The main 5 ways cancer kills you
Infection
Organ failure
Hemorrhage
Thromboembolism
Emaciation
225
What 3 things are in the lymph node hilum?
Efferent lymph vessels
Afferent arteriole
Efferent venule
226
Where are T cell precursors in the thymus? Where do they move?
Cortex and move inward as they mature
227
What 2 things make up the integrin?
CD18
CD11
228
Which cancer forms keratin pearls?
Squamous carcinoma of the lung
229
What is stage IV cancer?
Metastasis
230
What is stage III cancer?
Lymph node involvement
