Disease and Defense Unit 2-class of 2019 Flashcards

Question 1

Q

what are adaptations (in general)?

Answer

A

reversible changes in size, #, phenotype, metabolic activity, cell function, environment. Can be physiologic or pathologic

Question 2

Q

what are the 4 main adaptations (of cells)?

Answer

A

Think “Hham”: hypertrophy, hyperplasia, atrophy, metaplasia

Question 3

Q

hypertrophy

Answer

A

increase in cell size—> increase organ size (limit eventually reached and can no longer compensate—> injury). can be physiologic or pathologic. may be reversible. example: uterus in pregnancy, heart in hypertension.

Question 4

Q

Can hypertrophy occur with hyperplasia?

Question 5

Q

hyperplasia

Answer

A

increase in number of cells (response to stimulus/injury). physiologic=hormonal or compensatory. pathologic=excessive hormonal or GF stimulation (these are very “hyper” cells). increase in cell number. can be physiologic or pathologic. may be reversible. often driven by hormones/growth factors. May be associated with increased risk of neoplasia. eg: mammary gland in puberty, endometrial neoplasia

Question 6

Q

if stimulation is removed in pathologic hyperplasia, what happens?

Answer

A

abates. doesn’t happen with cancer

Question 7

Q

atrophy

Answer

A

decrease/shrinkage in size/function capacity of cell. physiologic=loss hormonal stimulation, decreased workload. pathologic=denervation or diminished blood supply.

Question 8

Q

mechanism of atrophy:

Answer

A

down with the protein synth and up with the protein degradation!!!!!

Question 9

Q

metaplasia

Answer

A

reversible change where 1 cell type is replaced by another (“it’s so meta!”). typically because 1 cell is sensitive to stress, and another is better able to handle it. change from benign differentiated cell type to another, usually in response to injury. may be associated with increased risk of neoplasia. “in between” state. best observed and most observed in epithelia. seems to have a “field effect”. eg: columnar to squamous metaplasia, barrett esophagus

Question 10

Q

what is metaplasia named for (the cells)?

Answer

A

what it ends up as

Question 11

Q

reversible cell injury

Answer

A

if damaging stimulus removed, you can heal if damage isn’t too badly progressed to severe membrane damage/nuclear dissolution

Question 12

Q

what classifies irreversible injury?

Answer

A

cell death! necrosis/apoptosis, other causes

Question 13

Q

cellular swelling is caused by what…?

Answer

A

failure of ion pumps in plasma-which disrupts ionic/fluid homeostasis.

Question 14

Q

what is fatty change?

Answer

A

accumulation lipid vacuoles in the cytoplasm of cells (especially those that do fat metabolism). Due to increased entry/synthesis of free Fa and decreased FA oxidation. non-specific, reversible.

Question 15

Q

intracellular changes with reversible injury:

Answer

A

plasma membrane alterations, myelin figures, dilation of ER, nuclear alterations

Question 16

Q

what are myelin figures?

Answer

A

phospholipid masses derived from damaged cell membranes

Question 17

Q

what are the 2 big irreversible cell injury morphologies?

Answer

A

necrosis and apoptosis

Question 18

Q

what are some intracellular changes associated with irreversible injury?

Answer

A

cytoplasmic changes (increased eosinophilia), loss of RNA basophilia in cytoplasm

Question 19

Q

what are some nuclear changes associated with irreversible injury?

Answer

A

breakdown of DNA and chromatin, kayorrhexis (pynknotic nuclear fragments), karyolysis (nucleus dissolution)

Question 20

Q

pynknosis is what?

Answer

A

nucleus shrinks, increased basophilia

Question 21

Q

List the 5 patterns of tissue necrosis:

Answer

A

“Cassie Left Connie For Frank”.

Caseous, Liquefactive, Coagulative, Fibrinoid, Fat

Question 22

Q

coagulative necrosis

Answer

A

GANGRENOUS!!!!!! (involves multiple layers). Architecture of tissue preserved for several days, dead cells are pale/ghost like, characteristic of infarcts, any white/yellow is still live tissue

Question 23

Q

liquefactive necrosis

Answer

A

seen in focal bacterial/fungal infections, fungal infections. microbes stimulate accumulation of inflammatory cells. leukocyte enzymes digest the bacteria. there are no histeocytes/giant cells unless responding to microbes

Question 24

Q

caseous necrosis

Answer

A

tuberculosis infections (and histoplasmosis). derived from white apron, necrotic area is fragmented/lysed cells. has histeocytes/giant cells.

Question 25

Q

granulomas inflammation

Answer

A

amorphous granular debris enclosed in inflammation border. histologically distinctive pattern of chronic inflammation. fibrosis often forms around it

Question 26

Q

fat necrosis

Answer

A

fat destruction due to activated pancreatic lipases. chest wall trauma, breast tissue, etc. fat hydrolyzed into free FA and precipitated with calcium into chalky, grey material

Question 27

Q

fibrinoid necrosis

Answer

A

immune rxn where complexes of antigens/antibodies are deposited into artery walls. deposited immune complexes combine with fibrin and produce bright pink/amorphous appearance on H&E

Question 28

Q

list the 6 mechanisms of cell injury:

Answer

A

ATP depletion, mitochondrial damage, influx of calcium, accumulation of ROS, increased membrane permeability, accumulation of damaged DNA/misfolded proteins.
“ROS CAn MEet MItch After Dinner.”

Question 29

Q

ATP depletion and cellular injury

Answer

A

Oxidative phosphorylation+ADP=ATP in mitochondria, or via glycolytic path in absence of O2. Tissues with greater glycolitic capacity can survive better. makes tissue susceptible to ischemic injury (think about DELICATE and not as renewable tissue)

Question 30

Q

mitochondrial damage and cellular injury

Answer

A

failure of oxidative phosphorylation means: ATP depletion, ROS forms, high conductance channels formed destabilizing mitochondria, releasing of proteins and apoptosis

Question 31

Q

influx of calcium and cellular damage

Answer

A

ischemia and toxins cause release from intracellular stores

Question 32

Q

accumulation of ROS and cellular damage

Answer

A

damage by free radicals via 2 paths:
1) all cells during REDOX rxn during mito respiration,
2) phagocytic leukocytes.
consequences=damage is based on removal rate. increased production=ineffective scavenging by enzymes=stress. Removal by spontaneous decay.

Question 33

Q

increased permeability of cellular membranes and cellular damage causes damage where?

Answer

A

Important sites of damage: mitochondria, plasma membrane, lysosome

Question 34

Q

spontaneous decay in ROS damage

Answer

A

SUPEROXIDE converts H2O2 by SOD. Decomposition to H2O by GLUTATHIONE, PEROXIDASE, CATALASE

Question 35

Q

what is apoptosis?

Answer

A

programmed cell death where cells activate enzymes to degrade cellular nuclear DNA and nuclear cytoplasmic proteins (fragment/fall off!!!!). Doesn’t illicit an inflammatory response

Question 36

Q

what are some physiologic causes of apoptosis?

Answer

A

programmed destruction (embryogenesis),
involution of hormone dependent tissues (hormone deprivation),
cell loss in proliferating cell=POP!!!,
elimination of used up cells,
elimination of self-reactive lymphocytes,
death from cytotoxic T-lymphocytes

Question 37

Q

what are some pathologic causes of apoptosis?

Answer

A

DNA damage with inadequate repair (eliminate instead of propagate),
accumulation misfolded protein (ER stress),
cell injury (viral infection, etc.),
pathologic atrophy in parenchymal organs after duct obstruction

Question 38

Q

what is the morphology of apoptosis?

Answer

A

picnotic nucleus that darkens (condensed chromatin), fragmentation, apoptotic bodies are phagocytosed or taken up by neighboring cells

Question 39

Q

what is the mechanism of apoptosis?

Answer

A

1) mitochondrial path and

2) death receptor

Question 40

Q

describe 3 things mitochondrial apoptosis has:

Answer

A

anti apoptotic mechanisms (BCL2, BCL-XL, MCL1), pro apoptotic mechanisms (BAX, BAK), these lead to activation of initiator caspases (8,9; executioner)

Question 41

Q

what is autophagy?

Answer

A

where a cell eats its own contents! Yum!. it’s an adaptive response/survival mechanism for times of deprivation. disregulated sometimes (cancer, disease, IDB, neurodegenerative disorders), role in host defense (degrades some pathogens: Mycobacteria, HSV-1, etc)

Question 42

Q

what are four main paths of abnormal accumulation of substances in a cell?

Answer

A

1) inadequate removal;
2) accumulation of abnormal endogenous substance,
3) failure to degrade due to inherited enzyme deficiencies,
4) deposition/accumulation of abnormal exogenous substances

Question 43

Q

hemosiderin

Answer

A

hemoglobin derived granular pigment. accumulates with excess of iron. found with Prussian blue

Question 44

Q

lipofuscin

Answer

A

wear and tear pigment. accumulates with age/atrophy. its a complex of lipid an dprotein

Question 45

Q

steatosis

Answer

A

accumulation of tryglycerides

Question 46

Q

cholesterolosis

Answer

A

deposition of cholesterol in macrophages in gallbladder

Question 47

Q

what is pathologic calcification?

Answer

A

abnormal deposition of calcium salts (and iron, magnesium, other minerals)

Question 48

Q

dystrophic calcification

Answer

A

dead/dying tissue. absence of systemic derangement in calcium metabolism. appears purple to pink.

Question 49

Q

psammoma body/calcification

Answer

A

sign of degeneration and cell turnover. laminate of calcification. seen in benign and malignant proliferations (meningioma, papillary thyroid carcinoma, serous carcinoma). outside of cell-aggregate of dead cells and contents.

Question 50

Q

metastatic calcification

Answer

A

seen in normal tissues. secondary derangement to calcium metabolism. (precipitates and deposits out of tissue). hypercalcemia, hyperparathyroidism, Paget disease, etc.

Question 51

Q

innate immune system

Answer

A

nonspecific defense mechanism. occurs immediately/very soon.

Question 52

Q

what are they physical barriers of innate immune system?

Answer

A

skin, mediators in the blood, immune system cells

Question 53

Q

adaptive immune system

Answer

A

antigen specific response. more complex-requires antigen processing. Specific cells must be made/designed for each antigen. Maintains memory cells for future encounters (for quick response). takes a while to develop!

Question 54

Q

acute inflammation: onset, cellular infiltrate, tissue injury/fibrosis, local/systemic signs

Answer

A

onset: fast (minutes, hours),
infiltrate: neutrophils,
tissue injury: mild/self limited,
local/systemic signs: prominent

Question 55

Q

chronic inflammation: onset, cellular infiltrate, tissue injury/fibrosis, local/systemic signs

Answer

A

onset: slow (days),
infiltrate: monocytes/macrophages/lymphocytes,
tissue injury: severe and progressive,
local/systemic signs: less prominent/may be subtle

Question 56

Q

list the 4 stimuli for acute inflammation:

Answer

A

Infection, Trauma, Foreign Material, Immune Rxn.

“I Try For My Immunity”

Question 57

Q

list some possible infections:

Answer

A

bacterial, viral, fungus, parasites, toxins

Question 58

Q

list some possible trauma:

Answer

A

mechanical, chemical, thermal, nuclear, direct physical/chemical damage to cells

Question 59

Q

list some foreign materials that could cause inflammation:

Answer

A

substance that directly stimulates inflammation and its associated “stuff”. microbes, etc.

Question 60

Q

list some immune reactions:

Answer

A

host/environment antigens cause inflammation,
immune reactions or hypersensitivity rxns,
inappropriate response to inflammation/environment.
These often persist, tend to be chronic.

Question 61

Q

inflammation receptors

Answer

A

pattern recognition receptors present on large variety of cells. they pick up stuff (microbe-derived substance, toxins, necrotic cell material, etc).

Question 62

Q

Toll Like Receptors (TLR)

Answer

A

10 receptors. they detect a variety of MICROBES (on plasma membrane, endosomes). TLR stimulated—> transcription factors—> mediators of inflammation and anti microbial products (stimulates inflammatory cytokines)

Question 63

Q

Inflammasome

Answer

A

complex of proteins that mediate cell response esp in response to dead/damaged cells or microbes. (stuff=uric acid, ATP, decreased K, DNA). receptors in cytoplasm=important stimulators. Activates capsize 1—> IL1-beta—> inflammation

Question 64

Q

Pro inflammatory receptors have what 3 locations?

Answer

A

plasma membrane, endosomes, cytosol

Answer 64

A

key component of reaction to bring cells and other material quickly to the site of injury/threat. this directly leads to many early clinical signs of infection

Answer 65

A

calor (warmth, increased flow), rubor (increased flow, congested capillary bed, erythema), tumor (permeability, exudate into tissue, swelling)

Answer 66

A

arterioles dilate, flooding capillaries. Histamine (mediator) acts on smooth muscle to stimulate the dilation (endothelial cells contract).

Answer 67

A

material is taken from the intravascular space and transported through the endothelial cells via vesicles

Answer 68

A

increased vascular permeability,
increased protein content,
increased cell content and inflammation and RBC,
high specific gravity

Answer 69

A

increased hydrostatic or decreased colloid osmotic pressure,
decreased protein content,
fewer cell content,
low specific gravity

Answer 70

A

result of increased permeability/leakiness of vessels related to inflammation—>proteins get pushed out!

Answer 71

A

filtering of fluid, result from cardiac failure. decreased blood protein (oncotic pressure) from liver disease can cause. also caused by heart failure. filtered fluid due to vessel being “tight”

Answer 72

A

accumulating edema and debris that inflammation produces

Answer 73

A

margination/rolling, adhesion, transmigration, chemotaxis “MATCh”

Answer 74

A

targeting certain areas for migration of leukocytes in 4 phases, low level of natural peripheral movement, but is first step of ACUTE inflammation

Answer 75

A

leukocytes accumulate on endothelium (laminar flow-slower/larger go to periphery). Vascular permeability thicker, blood moves slower.

Answer 76

A

stimulated endothelial cells have adhesion molecules with sugar affinity on leukocytes. endothelium induced to move these surfaces via chemical mediators. local tissues detect threat—>mediators released—>vessel is sticky

Answer 77

A

histamine—>p selectin. IL1—>E selectin

Answer 78

A

occurs when leukocytes reach area of activation that has been signaled by leakiness. alter interns on surface into a high-affinity state. (Icam-1 binds these). results in stable attachments sites of inflammation

Answer 79

A

YES! first margination, then adhesion

Answer 80

A

Think phantom of the opera-“Past the point of no return!!! No going back now!!!” after adhesion arrests leukocyte on endotheium. squeeze btw endothelial cells in venules (diapedesis).

Answer 81

A

secrete enzymes like collagenous to break up basement membrane of vessels

Answer 82

A

leukocytes move towards site of inflammation by following chemical gradients of greater density. start in vascular space—>diapedese—>move towards gradient. this is tied to the contractile elements of a cell, direction of greatest chemotactic density determines the movement.

Answer 83

A

Heck yes! bacterial products, cytokines, compliment proteins (C5), arachidonic acid metabolites (LTB4)

Answer 84

A

inflammatory cells

Answer 85

A

activate when encounter certain substances: microbial products, cellular debris, mediators, etc.

Answer 86

A

1) readily phagocytize material,
2) be poised to kill/degrade engulfed materials (nomnonmnom),
3) readily secrete material into extracellular environment to kill or degrade tissue,
4) produce inflammatory mediators to amplify inflammatory process

Answer 87

A

recognition/attachment of particle to leukocyte—> engulfment and formation of vacuole—> killing/degrading vacuolated material

Answer 88

A

1) receptors for specific products/microbes/necrotic cells,

2) receptors for opsonins

Answer 89

A

host proteins present in blood or produced locally that coat microbes (IgG, C3b, collectins)

Answer 90

A

SUPEROXIDE ION (toxic oxidizer)

Answer 91

A

HYDROGEN PEROXIDE

Answer 92

A

HYPOCHLOROUS RADICAL (strong oxidizer

Answer 93

A

OTHER LYSOSOMAL ENZYMES

Answer 94

A

neutrophil extracellular traps. they are nuclear chromatin that act as scaffolding with embedded antimicrobial compounds providing and area of antimicrobial material that traps microbes. it takes the nucleus, extrudes complex, traps microbes, kills them

Answer 95

A

resolution, chronic inflammation, scarring

Answer 96

A

only happens if the tissue can regenerate. occurs in a limited degree of injury (minimal damage). requires termination of inflammatory process

Answer 97

A

generally occurs when the offending agent not removed by acute inflammation so the system transitions to chronic. can be prolonged, followed by resolution or scarring. doesn’t always follow acute inflammation.

Answer 98

A

occurs when tissue can’t regenerate, after considerable destruction. results from tissue being filled in by connective tissue elements, can significantly impair function

Answer 99

A

tissue surrounding infectious agents, cleaning up necrotic tissue by inflammatory process may cause damage, inflammatory process directed against host tissue

Answer 100

A

often presented as sequential steps, but can occur w/ chronic inflammation. mononuclear cell infiltrate (cells with small round nuclei), tissue destruction, repair

Answer 101

A

persistent infections, immune mediated diseases, prolonged exposure to toxins

Answer 102

A

some infections difficult to eliminate or stimulate a response to—> associated with delayed hypersensitivity reaction

Answer 103

A

autoimmune diseases, allergic diseases (endogenous response)

Answer 104

A

exogenous substances that can’t be broken down/removed promote inflammation (constant low grade stimulation). endogenous substances may do this as well

Answer 105

A

blood monocyte. circulates for a day and gives rise to macrophages in tissues throughout body. sometimes given names specific to location (Kupffer cells in liver). All are same origin, basic function

Answer 106

A

ingest microbes/cellular debris. initiate tissue repair (fibrosis/scar)

Answer 107

A

endotoxin, IFN-gamma, foreign material

Answer 108

A

ROS, NO, lysozymal enzymes, proinflammatory cytokines

Answer 109

A

killing microbes, chronic inflammation

Answer 110

A

IL-4, IL-13 (from eosinophils, T-cells, mast cells)

Answer 111

A

growth factors for new vessels, fibroblast activation

Answer 112

A

tissue repair, fibrosis

Answer 113

A

barely noticeable in cytoplasm, involved large variety of inflammatory responses. many chronic disorders mediated by lymphocytes. activation is a function of adaptive immunity

Answer 114

A

TH1 CD4+ T lymphocytes secrete IFN-ɣ: activates classical pathway macrophages.
TH2 CD4+ T lymphocytes secrete IL-4, IL-5, IL-13: activates alternative pathway macrophages; also activates eosinophils.
TH17 CD4+ T lymphocytes secrete IL-17: recruitment of neutrophils and monocytes

Answer 115

A

bright red granules, bilobed nuclei. recruitment is similar to neutrophils, but includes specific chemokines (eotaxin)

Answer 116

A

parasitic infections (have major basic protein toxic to parasites), allergic reactions mediated by IgE

Answer 117

A

involved acute/chronic inflammation. network of cells in body, can quickly release mediators (histamine, arachidonic acid, etc), coated with IgE to trigger mediator release. well known for allergic involvement-wide distribution and quick response to infections

Answer 118

A

enlarged macrophages form a nodule, surrounded by lymphocytes. form around organisms and prevent their spread.

Answer 119

A

inflammatory reactions not eradicated by reactions (leprosy, tuberculosis), some immune mediated diseases (crohns), foreign material, sarcoidosis (last resort diagnosis)

Answer 120

A

TNF, IL-1, IL-6

Answer 121

A

vascular cells in hypothalmus are stimulated by pyrogens to produce prostaglandins (PGE2). Act locally to cause central increase of body temp. exogenous pyrogens cause leukocytes to release endogenous pyrogens (act on hypothalamus vasculature) and can also act directly on hypothalmus vasculature

Answer 122

A

IL-6 hepatocytes. produce several proteins in greater abundance. clinically used to detect and monitor progress of inflammatory processes.

Answer 123

A

C reactive protein (CRP), Serum Amyloid A (SAA)

Answer 124

A

binds RBCs to make them into stacks that sediment. this becomes the basis of the erythrocyte sedimentation rate (ESR) to test for inflammation

Answer 125

A

increased leukocytes in the blood. WBC increase systemically in inflammation. TNF and IL-1 cause more to be released from bone marrow. may see increased number of immature WBC (left shift of leukocytes).

Answer 126

A

colony stimulating factors (CSF). increase bone marrow production of leukocytes

Answer 127

A

increased nuetrophils, bacterial infection

Answer 128

A

increased lymphocytes, viral infection

Answer 129

A

increased eosinophils, asthma/parasitic infections

Answer 130

A

specific infections (eg: typhoid fever)

Answer 131

A

produced at site of inflammation or by the liver to be activated at site of inflammation. once they are released they have a short lifespan. they are activated by specific receptors, some have broad and non-specific effects

Answer 132

A

reformed for secretion, synthesized on demand

Answer 133

A

vasoactive amines, ARACHIDONIC ACID METABOLITES, platelet-activating factor, cytokines, ROS, NO, lysosomal enzymes, neuropeptides

Answer 134

A

COMPLIMENT, coagulation and kinin

Answer 135

A

histamine and serotonin. Stored in cells for quick release/repsonse.

Answer 136

A

vasoconstriction to aid in clotting, present in platelet granules

Answer 137

A

arterial dilator and endothelial contractor. Mast cells, basophils, platelets.

Answer 138

A

physical features (mechanical, temp), immune (IgE bind), compliment (C3a, C5a), histamine releasing proteins (from leukocytes), neuropeptides, cytokines (IL-1 or 8)

Answer 139

A

derived from cell membrane phospholipids, transformed into compounds that mediate inflammation and homeostasis. from leukocytes, mast cells, endothelium, platelets.

Answer 140

A

spontaneous decay and enzymes

Answer 141

A

1)cyclooxygenase (results in prostaglandins and thromboxanes), 2)lipoxygenase (results in leukotrienes and lipoxins)

Answer 142

A

vasodilation

Answer 143

A

vasoconstriction

Answer 144

A

vascular permeability. mediate specific functions of inflammation. LTB4=chemotactic for neutrophils. LTC4, LTD4, LTE4=vascular permeability

Answer 145

A

inhibit endothelial adhesion/chemotaxis. generated as leukocytes enter tissue. antagonize leukotrienes-anti inflammatory.

Answer 146

A

NSAIDs block cyclooxyrgenase, glucocorticoids block phospholipase A2 (shut down whole path)

Answer 147

A

prostoglandins contribute to pain and fever symptoms. presence of enzymes determines the compounds of a specific AA path.

Answer 148

A

polypeptides that function as mediators in innate and adaptive immune system.

Answer 149

A

TNF and IL-1

Answer 150

A

produced mostly in macrophages, mast cells, endothelial cells. stimulated by microbial products, immune complexes, endothelial cells. cause endothelial activation, induce systemic effects of inflammation

Answer 151

A

subset of cytokines. small proteins separated into 2 groups (CXC, CC) based on structure. function in chemotaxis, also activate leukocytes

Answer 152

A

chemotactic for neutrophils

Answer 153

A

chemotactic for variety of cells

Answer 154

A

IFN-γ, IL-12

Answer 155

A

stimulates classical macrophage activation

Answer 156

A

stimulates growth and function of T cells

Answer 157

A

released from activated neutrophils and macrophages. NADPH oxidase path. Superoxide ion changes to OH ion. can be reduced to a radical or converted to hypochlorous radical (BLEACH) vial myeloperoxidase in neutorphils.

Answer 158

A

free radical that can be used to kill microbes. mediator vasodilation (antagonizes platelet activation, reduces leukocyte recruitment/attachment). Made by Nitric Oxide synthase (NOS) from L-arginine.

Answer 159

A

induced by macrophages and endothelial cells. responsible for NO inflammation

Answer 160

A

constitutively expressed in endothelial cells

Answer 161

A

azurophil granules of neutrophils and granules of monocytes. contain enzymes that can kill microbes and digest ingested materials. can damage host tissues (acid proteases, neutral proteases are active outside cell).

Answer 162

A

in blood/body tissues to limit damage to host tissues. Alpha-1-antitrypsin (neutrophil elastase inhibitor-emphysema), alpha-2-macroglobullin (inhibits proteinases-eg collagenase)

Answer 163

A

initiate inflammation, active in vascular tone/permeability. active in lung and GI.

Answer 164

A

Substance P. secreted by nerves/inflammatory cells. binds neurokinin-1-receptor. generates pro inflammatory effects in immune and epithelial cells

Answer 165

A

large number of plasma proteins involved with inflammation nd immunity. opsonize pathogens and induce inflammatory response to fight infection. final complement forms MAC. increase vascular permeability and leukocyte chemotaxis

Answer 166

A

inactive. plasma. activated by proteolysis. once activated can proteolyses and amplify the reaction (self activate). Key factor is C3 converts cleaving C3 into a and b.

Answer 167

A

1) classical: fixation of C1 to antigen-antibody complex. 2) alternative: microbe cell wall components combine with plasma proteins. 3) lectin: plasma letting binds microbial mannose and stimulates classical path

Answer 168

A

C3a, C5a increase vascular permeability (stimulate mast cells to release histamine). C5a stimulates lipogenous path for AA metabolism. leukocytes are activated via C5a, 4a, 3a to increase endothelial adhesion. C3b is opsonin for enhanced phagocytosis. MAC.

Answer 169

A

C1 inhibitor, Decay accelerating factor (DAF), and factor H

Answer 170

A

an important clotting factor that activates the kinin system, leading to bradykinin (increases vascular permeability, dilation, pain). activates the clotting cascade!

Answer 171

A

an intermediate product that is chemotactic. it activates factor 7 but can self activate

Answer 172

A

leads to vascular permeability

Answer 173

A

binds protease activated receptors on endothelial cells, activating them. cleaves fibrinogen (to make fibrinopeptides) to increase vascular permeability (chemotactic). cleaves complement factor 5 to form factor 5a.

Answer 174

A

the fibrinolytic system (active inflammatory mediators)

Answer 175

A

factors serving to antagonize driving/facilitating mediators of inflammation to allow for a baseline. lipoxins, compliment regulatory proteins (C1 inhibitor), IL-10, TGF-beta

Answer 176

A

antagonize leukotreines (anit-inflammatory mediator)

Answer 177

A

secreted by macrophages. down regulates activated macrophages

Answer 178

A

promotes fibrosis. anti-inflammatory as process moves to scarring.

Answer 179

A

restoration of tissue architecture and function if possible after injury

Answer 180

A

proliferation, integrity

Answer 181

A

remnants of injured tissue (to restore normal structure), vascular endothelial cells (new vessels for repair), fibroblasts (source fibrous tissue to make scar)

Answer 182

A

labile (continuously dividing), stable, permanent

Answer 183

A

continuous turnover from stem cells and proliferation of mature cells. injured cells replaced by residual cells and stem cells if basement layer is intact.

Answer 184

A

bone marrow, surface epithelia: skin, oral cavity, GI, ducts, urothelium, etc

Answer 185

A

quiescent tissue (minimal replication even though capable in response to injury/loss). exception is liver since has robust capacity to regenerate. most have limited regeneration capacity.

Answer 186

A

parenchyma of most solid organs: liver, kidney, pancreas. also endothelial cells, fibroblasts, smooth muscle

Answer 187

A

terminally differentiated, can’t proliferate. limited stem cell replication and differentiation that is insufficient for regeneration. forms scars instead

Answer 188

A

neurons, cardiac muscle

Answer 189

A

yes! most tissues have some regeneration and scar formation

Answer 190

A

characterized by self renewal and asymmetric replication (can make daughter cells that have 2 fates), embryonic and adult

Answer 191

A

most undifferentiated, present in inner cell mass of blastocyst. can form ecto,endo, meso

Answer 192

A

tissue stem cells. less undifferentiated than ES cells, found in organ or tissue. self renewal capacity. more restricted lineage potential. important for tissue homeostasis

Answer 193

A

skin: adjacent epithelial cells, hair follicle: follicles in skin

Answer 194

A

proteins that stimulate survival/proliferation of particular cells. may promote migration, differentiation, other cell responses.

Answer 195

A

macrophages, lymphocytes, or parenchymal/stromal cells

Answer 196

A

directly in cell, adjacent cells, distance/remote cells

Answer 197

A

complex of several proteins that assembles into a network surrounding cells and makes up a large portion of any tissue. regulates proliferation, movement, differentiation of cells. is required for tissue regeneration and if it is damaged only a scar can form.

Answer 198

A

1) fibrous structural proteins,
2) water hydrated gels,
3) adhesive glycoproteins

Answer 199

A

interstitial matrix and basement membrane

Answer 200

A

spaces btw connective tissues. made by mesenchyme. made of fibrillar and non fibrillar collagens. scaffolding (collagens, ellastins, proteoglycans)

Answer 201

A

beneath epithelial, endothelial, smooth muscle cells. made by epithelium and mesenchyme. made of amorphous non-fibrilar type 4 collagen and laminin

Answer 202

A

robust. 40-60% of liver can be removed for transplant, can regenerate. can also regenerate if other injury/insults happen if framework intact. priming—> g0—> g1—> proliferation—> regeneration!

Answer 203

A

results when repair not possible by regeneration alone. replaces non-regenerated cells with connective tissue. sometimes just scar or combo of scar and cell regeneration

Answer 204

A

tissue injury is severe or chronic, parenchymal cells and epithelia are damaged, non dividing cells are inured

Answer 205

A

angiogenesis, migration and proliferation of fibroblasts and deposition of connective tissue and agencies, maturation and reorganization of fibrous tissue

Answer 206

A

vasodilation (triggered by NO), permeability by VEGF, separation of pericytes from albumin surface, sprout and migration to area of injury, proliferation, remodeling, recruitment of periendothelial cells, suppression

Answer 207

A

locally procuced cytokines and GF: PDGF, FGF-2, TGF-BETA!!!!!

Answer 208

A

MMP. matrix metalloproteinases. produced by a variety of cells, include interstitial collagenases, gelatinases, stromelysins. important for remodelling

Answer 209

A

impair collagen synthesis if shot tin protein and Vitamin C

Answer 210

A

delay repair if you have diabetes, are on glucocorticoids (inhibit TGF-beta production and diminish fibrosis)

Answer 211

A

ischemia, venous drainage (poor perfusion if lack of resources). Thrombosis, arteriosclerosis and artherosclerosis, varicose veins

Answer 212

A

if the inciting insult has been terminated or persists, if a new insult (infection) has been introduced

Answer 213

A

hypertrophic scar (regresses from going outwards originally), keloid (does not regress)

Answer 214

A

goes outside the bounds of initial repair. occurs in groups and families. pink/ropy collagen

Answer 215

A

look like keloids, but they regress. can cause contracture

Answer 216

A

epithelial regeneration is principal repair mechanism. superficial, clean wounds, not large. fibrous but not contracture. neutrophils—> fibrin clots—> angiogenesis—> granulation—> epithelial regeneration

Answer 217

A

combination of regeneration and scarring. contracture occurs via myofibroblasts to contract tissue together. inflammation is more intense, larger area to fill in and regrow

Answer 218

A

drugs whose therapeutic action is to reduce pain and inflammation caused by COX1 and 2, as well as decrease production of inflammatory prostaglandins and thromboxjnes

Answer 219

A

yes. prostaglandins mediate physiologic maintenance functions, and inhibition can cause predictable side effects in tissues (we know what it will do though so that’s good)

Answer 220

A

analgesia, antipyretic effect, anti inflammatory, antithrombogenesis

Answer 221

A

inhibits inducible COX2 at injury site. low to moderate intense pain relief. intermediate dose, prn dosing.

Answer 222

A

inhibits inducible COX2 in hypothalmus. fever reduction! (anti-pyretic, anti fire!) intermediate dosing, prn dosing.

Answer 223

A

inhibition of inducible COX2 at sites of inflammation. treats RA. hi doses, scheduled dosing, based on half life

Answer 224

A

inhibits COX1 in platelets. primary and secondary MI risk reduction. low dose, daily.

Answer 225

A

inhibits constitutive COX1 in gastric cells=ulceration, bleeding, nausea

Answer 226

A

COX1 inhibit in platelets

Answer 227

A

inhibition of COX 1, 2 in kidney cells=acute renal failure and interstitial nephritis

Answer 228

A

inhibition of COX2 in smooth m.= interference uterine contractions late term pregnancy

Answer 229

A

unopposed inhibition of COX2 in vascular endothelial cells=potential for increased cardiovascular events, including MI and stroke

Answer 230

A

reversible, COX1 AND 2. chemical classes are: “SOAPPy” (Salicylates, Oxicam derivatives, Acetic/carboxylic acids, Propionic acid derivatives, PYrazolone derivatives)

Answer 231

A

analgesic, antypyretic, anti-inflammatory

Answer 232

A

analgesic, antipyretic, anti inflammatory. more potent/longer lasting than aspirin, serious toxicities with misuse/chronic use

Answer 233

A

analgesic, antipyretic, anti inflammatory. fewer toxic rxns than pyrazolone, but many more adverse rxns related to idomethicin. limited generally to arthritis that don’t respond

Answer 234

A

anlagesic, antiipyretic, anti inflammatory. potent, long half life (15-50hrs)

Answer 235

A

analgesic, antipyretic, anti inflammatory. tolerated well, some OTC

Answer 236

A

NO inhibition COX1, 2 in PERIPHERY. inhibits COX2 in CNS. analgesic, antipyretic properties. less GI side effects

Answer 237

A

Seslective, reversible COX2 inhibition. analgesic, antipyretic, anti inflammatory. less GI side effects.

Answer 238

A

irreversible inhibition of COX1, 2. analgesic, antipyretic, anti-inflammatory, antithrombotic

Answer 239

A

ibuprophen, naproxen, ketoprofen

Answer 240

A

anti inflammatory, antipyretic, analgesic effects. rapidly/completely absorbed (>90% protein bound, renal excretion or liver metabolism). as effective as ASA or acetaminophen for mild/moderate point.

Answer 241

A

interfere with gastric cytoprotection via COX1 PGE sytnesis—> sypepsia and gastric ulceration. lowest risk with ibuprophen, highest with naproxen. food or antacids can help. PPI protect against gastroduodenal toxicity

Answer 242

A

interfere with platelet aggregation by inhibition cox1 thromboxane a2 synthesis (promotes bleeding). effect is 4-7 days ( life of platelet). should keep patients on regular NSAID use off of anticoagulants or vice versa

Answer 243

A

cause renal vasoconstriction by inhibiting COX1, COX2 PGE synthesis and loss of vasodilator actions-reversible renal insufficiency. can cause fluid retention, which can exacerbate heart failure. avoid if hypertension if diabetes, ckd, heart failure. lowest cardiovascular risk with naproxen.

Answer 244

A

all possess anlageisc, antypyretic anti inflammatory action. selectively reversible for COX 2 over 1 by 5-7 fold for celexoib. well absorbed and well exreted. metabolized by cyp2c9, long half life. used for RA, osteoarthritis, acute pain. less gastroduodenal toxicity to doses that provide pain relief than non selective NSAIDS. could reduce antithrombotic PGI2 activity. increases risk of CVD and HF in dose dependent manner. can precipitate acute renal failure, avoid use in at risk patients. can trigger sulfa allergy

Answer 245

A

equal to aspirin as analgesic/antipyretic. less anti inflammatory properties, possibly selective for inhibition of CNS prostaglandin synthesis. mild to moderate pain. inadequate alone for inflammatory conditions. peak absorption is in 30-60 min, related to gastric emptying. metabolized in large doses=liver toxic (depletes glutathione stores). hepatotoxicity is biggest and most common concern. limit to less than 4000 mg in 24hrs.

Answer 246

A

inhibits COX1 and 2. reduces mild to moderate pain of inflammatory origin. less effective in visceral pain. initial RA therapy and other inflammatory conditions, reduces elevated body temp, inhibits platelet aggregation. rapid absorption from small intestine. GI irritation minimized if pH >3.5. high plasma protein binding-may lead to displacement. avoids in: ulcers, alcoholics, older NSAIDs (warfarin), pregnancy, chronic renal insufficiency, asthma.

Answer 247

A

once frequent in children. mild is headache, dizzy, tinnitus, visual disturbances, mental confusion, drowsiness, sweating, thirst, hyperventilation, diarrhea. acute is: vomiting, fever, sweating, respiratory alkalosis, metabolic acidosis, death

Answer 248

A

critical enzyme in path for production of prostaglandins and thromboxanes from arachidonic acid. PGG/PGH synthase. no drugs currently inhibit isomerases/synthases.

Answer 249

A

cytokines, shear stress, GF, or up regulated as needed or for specialized functions. located inflamed/activated tissues.

Answer 250

A

enhance edema formation, leukocyte infiltration via vasodilation

Answer 251

A

increase heat generation and decrease in heat loss

Answer 252

A

renal adaptation to stresses via maintenance of renal blood flow. most critical in elderly

Answer 253

A

potential side effects: GI ulceration, prolonged bleeding time, acute renal failure

Answer 254

A

therapeutic actions (relief pain, fever reduction, inflammation reduction), potential side effects (acute renal failure, thrombotic events, prolonged gestation

Answer 255

A

enzyme in path for production of leukotrienes from AA. LTB4—> mast cells, eonsinophils, basophils, macrophages—> becomes CysLTs LTC4, LTD4, LTE4—>mediated by receptors.

Answer 256

A

neutrophil chemotaxis, aggregation, transmigration through endothelium

Answer 257

A

increased vascular permeability, bronchoconstriciton, vasoconstritction. role in asthma, psoriasis, arthritic process.

Answer 258

A

involved in carb and protein metabolism and anti-inflammatory response. cortisol is prototype hormone. only glucocorticoids have anti-inflammatory activity

Answer 259

A

involved sodium retention. aldosterone is prototype hormone

Answer 260

A

increased release occurs in concert with cortisol, but not aldosterone. DHEA and androstenedione have weak androgen activity, some is converted to testosterone and estradiol outside of adrenals

Answer 261

A

ACTH release controlled by corticotropin-releasingg factor from hypothalmus. glucocorticoids and androgens are controlled by AcTH action last adrenal cortex.

Answer 262

A

entrained by higher neuronal centers that release CRH from hypothalmus in response to sleep wake cycles

Answer 263

A

endogenous hormones and exogenous agents used in therapy. hypothalmus and pituitary decrease ACTH release and steroidogenesis.

Answer 264

A

chronic use of pharmacologic doses of glucocorticoids

Answer 265

A

substrate. rate limiting is cholesterol—>pregnelonone. ACTH stimulates this in zone fasted and reticularis. inhibited by metyrpone and mitotane

Answer 266

A

zona glomerulosa.

renin angiotensin system stimulates conversion of cholesterol to pregnenolone and cortiosterone to aldosterone.

Answer 267

A

most actions are mediated by widely distributed glucocorticoid receptors. cortisol as CBG enters cell—> binds to systolic receptor to release Hsp90 for dimerization of S-R complex (transcription regulated)—> effects on protein synthesis result in delayed onset

Answer 268

A

YES! ACTH pulses govern cortisol changes (peak post mea and in AM)

Answer 269

A

via the liver.

Answer 270

A

• Diurnal rhythm of basal steroidogenesis,
entrained by higher neuronal centers that
release CRH from hypothalamus in response to
sleep-wake cycles —>ACTH release —>cortisol
release
• Negative feedback regulation by circulating
corticosteroids (both endogenous hormones
and exogenous agents used in therapy) at the
hypothalamus and pituitary decreases ACTH
release and steroidogenesis.
NOTE: Chronic use of pharmacologic doses
of glucocorticoids can suppress the HPA axis
and result in adrenal atrophy and insufficient
adrenal response to environmental stressors
—> adrenal crisis.
• Stress (injury, hemorrhage, severe infection,
surgery, hypoglycemia, cold, pain, fear) can
override negative feedback and produce
marked increases in steroidogenesis.

Answer 271

A

structural changes can be made to produce glucocorticoid drugs with altered protein binding, prolonged half life, separation of mineralocorticoid and glucocorticoid activity. Carbohydrate stimulate gluconeogenesis—> increased blood glucose (increased insulin release)—> gluconeogenesis—> liver glycogen deposition. protein increased aa uptake into liver/kidney—> decreased protein synthesis—> net aa transfer from muscle to liver (muscle wasting). lipid inhibit uptake glucose by fat—> lipolysis—> lipogenic effect in central tissue. net physiologic result: maintenance of glucose supply to brain. anti inflammatory effects (decreased synthesis of inflammatory and immune mediators), immunosuppressive effects (suppress t cell activation, decreased healing/immunity), reduced vasodilation, reduced accumulation of activation of cells (decreased leukocytes in acute inflammation, decreased monocytes/lymphocytes in chronic inflammation, decreased clonal expansion T/B cells.

Answer 272

A

Common use in physiologic doses for replacement therapy and emergencies; glucocorticoid and mineralocorticoid actions [1:1]; administered orally and parenterally

Answer 273

A

Most commonly used oral agent when steroid burst therapy desired; glucocorticoid and mineralocorticoid actions [13:1]; activated to prednisolone in liver. NO topical activity, not activated until first pass hepatic metabolism.

Answer 274

A

Used if parenteral administration desired for steroid burst (no better than oral prednisone in acute exacerbations of asthma); minimal mineralocorticoid action. Oral (Medrol) and parenteral (Solu-Medrol)

Answer 275

A

Most potent anti-inflammatory agent, used in cerebral edema, chemotherapy-induced vomiting; no mineralocorticoid action, greatest suppression of ACTH secretion at pituitary.

Answer 276

A

Potent systemic agent - excellent topical activity; no mineralocorticoid action

Answer 277

A

Consider seriousness of disease, minimal amount for desired effect, duration of therapy.
Always reduce dosage as soon as therapeutic objectives are obtained. If using large doses, advisable to use shorter-acting agent with little mineralocorticoid effect. Alternate day schedule can minimize adverse effects (lessens growth-suppressive effects
because anti-inflammatory actions apparently outlast suppressive effect on HPA axis); make gradual transition to alternate day schedule after control of disease achieved. Terminate administration gradually if taken longer than 7-10 to 28 days, otherwise may cause severe rebound of disease or symptoms of adrenal insufficiency (adrenal crisis).

Answer 278

A

aldosterone binds to cystolic receptor, migrates to nucleus to induce mRNA formation to synthesize proteins. insertion of protein into membrane increases sodium reabsorption, increased secretion of H and K.

Answer 279

A

mineralocorticoid=salt retaining action at kidney. glucocorticoid=metabolic effects.

Answer 280

A

liver: 11beta-HSD1 converts cortisone to cortisol (activating. also prednisone to prednisolone). kidney 11beta-HSD2 converts cortisol to cortisone (inactivating). fetus placental 11beta-HSD2 is active but not HSD1 (liver isn’t functional), so use agent that is poor substrate for 11betaHSD2

Answer 281

A

nonsteroidal anti inflammatory drugs, glucocorticoids, disease modifying antirheumatic drugs (DMARDs)

Answer 282

A

NSAIDS. then DMARDS are added when the diagnosis is certain

Answer 283

A

low dose glucocorticoids. also used as adjunctive therapy when active disease persists through DMARDS

Answer 284

A

na and h20 retention—>edema—> increased BP, hypokalemia

Answer 285

A

glucose intolerance, mood changes, insomnia, GI upset

Answer 286

A

iatrogenic cushings syndrome, hypothalmic-pituitary-adrenal axis suppression, mood disturbance, impaired wound healing, increased susceptibility to infection

Answer 287

A

osteoporosis, posterior capsular cataracts, skin atrophy or loss of collagen support, growth retardation, peptic ulceration

Answer 288

A

hydrostatic and osmotic forces are nearly balanced. want a controlled movement of fluid from tissues into the body cavities. eg: if high capillary hydrostatic pressure fluid and salts into the interstitial space. venous area has concentration of proteins to pull back in. usually fairly equal pressure, only a small amount of fluid is leftover and collected by the lymph

Answer 289

A

extravasation (buildup of fluid in tissues—>edema, and natural spaces—>effusion). due to decreases in plasma oncotic pressure, increased permeability, lymph drainage exceeded.

Answer 290

A

vascular wall=intact. increased hydrostatic pressure, reduced oncotic pressure. usually just fluid without extra proteins and such

Answer 291

A

increased permeability of vascular wall. inflammation—> endothelial cells contract to make small gaps. direct damage to endothelial cells. proteins move across into interstitial space. can cause damage b/c things moving across that shouldn’t be

Answer 292

A

ultrafiltrate of plasma (increased hydrostatic pressure and/or reduced oncotic pressure).
less than 1, less than 3, less than 0.5, less than .6,
greater than 0.5, few WBC.
essentially: less (except glucose)

Answer 293

A

increased vessel permeability due to inflammation.
greater than 1, greater than 3, greater than .5,
greater than .6, less than .5, many WBC.
essentially: more (except glucose)

Answer 294

A

too much blood volume systemically or in a specific area.

Answer 295

A

physiologic: active! (inflammation, exercise, etc.).
arteriolar dilation,
oxygenated blood: red

Answer 296

A

pathologic: passive.
impaired venous outflow (obstruction causes backup into capillaries/arterioles).
deoxygenated blood: pale or red/blue.
low nutrient/oxygen blood that can’t move.
get ischemia of adjacent tissue since not getting enough oxygen

Answer 297

A

heart, kidney, liver

Answer 298

A

mostly due to scar tissue. not good output=peripheral tissue is not perfused well. fluid buildup in lungs. Kidney hates this, not enough fluid in vasculature so it holds onto fluid, dilutes out proteins and decreases oncotic pressure. fluid gets stuck in legs and move up the body from there. Lungs and Legs and Kidney

Answer 299

A

backs up into venous system. liver/portal circulation backs up you get portal congestion/liver congestion. oral system from gut goes to liver/spleen. fluid backs up into spleen. GI tract varies-dilated veins. then lots of fluid in organs, moves out of serosal surfaces—>acites. venous to liver to spleen to gut to organs to acites

Answer 300

A

blood outside of the vasculature into surrounding tissue. due to vessel damage (platelets and coag. factors can’t fix it). commonly due to trauma. impaired integrity of vessel walls, can be fixed if small but otherwise not. can’t keep up with constant capillary damage. Concern is WHERE damage is occuring. low level function of platelets, low level function of coagulation factors

Answer 301

A

small, pinpoint hemorrhages. tiny capillary breaks

Answer 302

A

bruise 1-2 cm

Answer 303

A

within tissue. placental abruption is example

Answer 304

A

builds up in flowing blood occurs in layers (tell if pre/post mortem). out of control is when layers keep building up and up. layers=lines of Zahn (platelet, red cells, platelet, red cells, etc.) can be driven by Factor 5 leiden.

Answer 305

A

used for thrombosis. Endothelial injury, abnormal blood flow, hypercoagulability

Answer 306

A

most common type of embolus. largely driven by stasis. DVT (immobility: recent surgery, estrogen, pregnancy/post partum, previous/current cancer, coagulation abnormalities, limb trauma/orthopedic procedures, obesity).

Answer 307

A

fluid/gas/solid mass floating in blood that shouldn’t be! pro-coagulant states push this. travels through big vessels to small ones of the pulmonary vessels. severity depends on what is blocked and how large the block is

Answer 308

A

not typically since flow is really fast

Answer 309

A

yes! initially starts with too much clotting, something in vessels floats around in bloodstream damaging vessels. continued vessel damage can lead to lack of sufficient platelets/clotting factors, so you bleed. otherwise issues can lead to thrombosis.

Answer 310

A

lots of little clots. symptoms from multiple organ systems (respiratory insufficiency, MSC, convulsions, acute renal failure, peticiae/purpura, GI, oral hemorrhage). shock. hemolytic anemia, thrmobocytopenia, low fibrinogen, elevated D-dimer and other fibrin degradation products

Answer 311

A

tissue death (necrosis) caused by vessel occlusion. typically coagulative necrosis caused. liquefactive necrosis is caused in the brain. damaged tissue gets replaced by scar tissue (generally), doesn’t work so well anymore…

Answer 312

A

dense tissue where you block off an artery. single blood supply. no reperfusion. dense tissue.

Answer 313

A

involved blood flow. temporarily block off, it comes back and you get hemorrhage. dual blood supply. reperfusion. loose tissue.

Answer 314

A

not enough blood, heart isn’t pumping enough blood to tissues. circulating blood volume is inadequate to perfuse tissues (can lead to multigrain dysfunction/damage).

Answer 315

A

myocardial pump failure. myocardial damage, extrinsic compression, outflow obstruction

Answer 316

A

low blood volume. severe dehydration, hemorrhage, burns

Answer 317

A

YES! low cardiac output+low BP=vasoconstriction, increased heart rate, recall conservation of fluid. skin is cool and pale, tachycardia, low urine output

Answer 318

A

type of shock we go into due to significant inflammatory shock. eg: septic shock (microbial infection, subset of SIRS). often not responsive to IV fluids. arterial vasodilation, vascular leakage, venous blood pooling

Answer 319

A

early on=highly orchestrated, dynamic program. results in formation of specialized tissues, organs, systems. very dynamic state

Answer 320

A

dramatic change in: proliferation (1 to billions), death (apoptosis), differentiation (totipotent—>organs/tissues), programmed cell death creates spaces, cell migration, cell-cell interactions

Answer 321

A

highly orchestrated, static program that provides optimal function of specialized tissues/organs/organ system. once you have adult, goal is to NOT proliferate, resulting in functional organs

Answer 322

A

constant turnover (benign and malignant neoplasm). skin, gut, epithelia, hematopoietic system

Answer 323

A

normally little/no turnover. capacity to turnover if needed. hepatocytes, liver

Answer 324

A

little to no proliferative capacity. brain development = post mitotic. CNS neurons, cardiac muscle

Answer 325

A

physical environment, infectious agents, inhaled/ingested substances

Answer 326

A

circulating factors, hormones, cytokines

Answer 327

A

extracellular matrix, stroma, growth factor, inflammatory mile

Answer 328

A

differentiation program. age of cell

Answer 329

A

when homeostatic balance is disturbed, pathology results.

Answer 330

A

hypertrophy, hyperplasia, neoplasia

Answer 331

A

new formation. progressive, unchecked increase in cell number. non invasive, non metastatic=benign. clonal process. pathologic and irreversible. “tumor”. disruption of normal homeostatic mechanisms

Answer 332

A

altered cell-autonomous mechanisms (activate oncogenes, inactivate tumor suppressor), cell non autonomous mechanisms (altered microenvironment: contribution of immune system can be important driving force. altered macroenvironment: breast cancer is example, hormonal force if counteracted impacts tumor growth)

Answer 333

A

don’t invade/metastasize. caused injury via compression/interference. treatment is surgical in most cases. tumor in essential spot, nowhere for organs to go (brainstem) can be fatal even though not invading. circumscribed/encapsulated. necrosis uncommon

Answer 334

A

invade and METASTASIZE. cancer. cause injury with local tissue destruction and distant dissemination and tissue destruction. clinically very significant. how most cancers kill you. invasive, necrosis common

Answer 335

A

relatively well differentiated. low rate cell turnover. cytologic uniformity. boundary btw. tumor and adjacent tissue maintained

Answer 336

A

variable differentiation. high rate of cell turnover. cytologic pleomorphism (cells differ markedly). loss of boundary btw tumor and tissue

Answer 337

A

epithelial, mesenchymal

Answer 338

A

epithelial (carcinoma, subset adenocarcinoma), mesnchymal (sarcoma), hematopoietic (lymphoma, lukemia)

Answer 339

A

treated by surgical resection alone. may recur. do not progress to malignancy except for benign, premalignant neoplasms (colonic adenoma)

Answer 340

A

cancer cells change over time (neoplasm/tumors). heterogeneous population of cells, makes targeted therapies difficult. ongoing genetic alterations+selection=clonal evolution

Answer 341

A

carcionomas (cancers of epithelia)

Answer 342

A

disordered growth. applied to epithelia, hallmark of early premalignant neoplasia. lose cytologic uniformity, lose normal histologic maturation, loss of architectural orientation. usually given a grade (low grade=less abnormal)

Answer 343

A

looks like cancer but can’t yet demonstrate invasiveness

Answer 344

A

degree of histologic differentiation. low grade-more differentiation, greater resemblance to normal. higher grade-less differentiation and resemblance to normal. grading scheme varies by tumor. low mitotic activity-low grade. can be predictive of biologic behavior, overall less reliable than disease stage

Answer 345

A

N and M involvement of the TNM stage scale. lowest T stage is non-invasive. the deeper the tumor invades, the worse the prognosis, so higher T stage is worse prognosis. goes up with lymph involvement

Answer 346

A

childhood neoplasms arise out of developing tissue-so they are different. origin n developmental (proliferative/migratory) precursors. recapitulate aspects of developmental program of tissue of origin. short latency and early metastasis. fewer mutations, prominent role for oncogenic fusions and epigenetic dysregulation. relative chemosensitivity

Answer 347

A

invasion and metastasis.

Answer 348

A

infiltration of adjacent tissues by malignant cells

Answer 349

A

transfer of malignant cells from primary site to non -connected/secondary site. discontinuous with primary tumor

Answer 350

A

pre invasive stage. stays above basement membrane. common in skin, breast, other sites. precursor to cancer

Answer 351

A

poorly. why it got name cancer (crab). invasive and can penetrate organ walls. surgical resection is difficult/impossible

Answer 352

A

1) direct seeding of body cavities/surfaces; 2) lymphatic spread; 3) hematogenous spread.

Answer 353

A

invasion (through basement memb./ECM), intravasation (get into blood/lymph), extravasation (exit vessel at new site), colonization (grow in new site)

Answer 354

A

when conditions are crowded/harsh/ there is waste buildup.

Answer 355

A

it has the capacity to modify cellular metabolism, it can evade immunological destruction (EMERGING hallmarks). It also has genomic instability and inflammation from immune cells can become tumor promoting (ENABLING CHARACTERISTICS).

Answer 356

A

carcinoma cells must breach the basement membrane, traverse the connective tissue, intravasaste.

Answer 357

A

Invasion! loosens up E-cadherin, degrades ECM, attaches ECM components, the cells migrate

Answer 358

A

they alter molecular adhesions. Ecadherin is down regulated, which facilitates detachment.

Answer 359

A

proteolytic enzymes are secreted or stromal cells are induced to make them. Matrix Metallo Proteases (MMPs) remodel insoluble components, and release ECM sequestered growth factors. when collagen is cleaved, proteoglycans have chemotactic, angiogenic, and growth promoters that get released

Answer 360

A

ameboid migraion or by cutting basement with proteases

Answer 361

A

tumor cells are resistant to apoptosis. cleavage of basement membrane allows for new binding sites that stimulate migration. receptors are not as important in cancer cells as in normal cells for maintaining the cells in a resting state

Answer 362

A

cleavage products of matrix components and IGF have chemotactic tumor activity. movement can be potentiated by tumor cell derived cytokines like autocrine motility factors. move collectively, mesenchymally, ameboid

Answer 363

A

it’s invasive! E cadherin is lost through: LOH, inactivation mutation, silencing, repression

Answer 364

A

SNAIL, TWIST, ZEB 1/2

Answer 365

A

palatogenesis, neural crest formation and movement, cardiac valve formation, myogenesis

Answer 366

A

downregulation epithelia proteins (ecadherin, cytokeratins). upregulation mesenchymal proteins (vimentin, fibronectin, n-cadherin, motility/invasiveness, increased protease secretion, fibroblast-like morphology

Answer 367

A

ECM+growth facors+ fibroblasts + immune cells. cross talk between these. not a static barrier, an area instead where reciprocal signaling can affect tumor suppression, promotion, progression

Answer 368

A

destruction!!!! by: mechanical shear stress, apoptosis by adhesion loss (can resist), immune system defenses. Typically they bind/aggregate to enhance survival/implantability. can bind and activate coagulation factors.

Answer 369

A

adhere to endothelium, egress through basement membrane via adhesion molecules

Answer 370

A

found in tumor margin. they help tumors intravasate into their new tissue home

Answer 371

A

seed and soil theory (needs of cancer cell for specific environment), and the mechanical arrest theory (cells arrest in first capillary bed encountered). these theories are not mutually exclusive.

Answer 372

A

no….tumor cells shed each day can be detected in the bloodstream. to compensate they can lie dormant. it seems that tumor cells secrete cytokines, growth factors, ECM molecules that act on stream cels that make a metastatic site habitable for cancer cells

Answer 373

A

invasive masses which interfere with normal function

Answer 374

A

“paraneoplastic syndrome” paracrine/endocrine effects. occur in 7-15% of patients

Answer 375

A

consequence of cancer presence, but not due to local present of cancer cells. neither direct or indirect cuase. thought to be the result of hormones/cytokines secreted by tumor cells and or immune responses the tumor triggers. can trigger: ectopic hormone production, cutaneous lesions, arthropathies, myopathies, myopathies, neuropatheis, thromboses, nephrosis, cachexia, DIC

Answer 376

A

in order: infection, organ failure, thromboembolism, hemorrhage, emaciation

Answer 377

A

80%. this is shown by regional differences in cancer rates, worldwide differences in cancer rates, and especially shown when migration to a new country happens (within a few generations you switch to being at risk for THAT countries cancers)

Answer 378

A

that is unknown. Tobacco causes 30% of all cancer deaths (with 85% of lung carcinoma related to tobacco use).

Answer 379

A

cancer of oral pharynx, larynx, pancreas, bladder, esophagus.

Answer 380

A

men=lung cancer (34% of cancer deaths) then prostate (12%) then colo/rectal (11%). women=lung (21%), then breast (18%), and colon (13%)

Answer 381

A

1/2 for men and 2/5 for women

Answer 382

A

in the 7th/8th decades

Answer 383

A

2-5% lower than US rates recently. in the last decade, its 10-13% lower

Answer 384

A

breast in women, prostate in men.

Answer 385

A

Kenneway and Heiger.

Answer 386

A

Berenblum

Answer 387

A

1) polycyclic aromatic hydrocarbons;
2) aromatic amines;
3) nitrosamines;
4) aflatoxins. all must be activated to a carcinogenic form by microsomal enzymes (cytochrome P450).
“PAANA-cotta is delicious, but may be a carcinogen!”

Answer 388

A

from incomplete combustion of fossil fuels. they become the diol epoxide

Answer 389

A

industrial and consumer products. N-hydroxylation and sulfating are required.

Answer 390

A

when 2 amines in food react with nitrous acid in stomach. hydroxylation leads to carbonium intermediate.

Answer 391

A

moldy grains and ground nuts, particularly when no refrigeration. produced by aspergillum flavus. microsomal expoxidation required

Answer 392

A

chemical carcinogens are usually metabolized by microsomal enzymes to be active. the metabolite is an electrophile. the electrophilic species can modify protein, RNA, and DNA

Answer 393

A

alkylating agents (n-mustards, chemotherapeutic agents). acylating agents (dimethylcarbamyl chloride)

Answer 394

A

these bulky adducts cause mutations (eg: mispairing, frameshift)

Answer 395

A

metal vapors, arsenic, thorotrast (liver cancer from radiology), exposure to vinyl chloride, asbestos, benzene exposure (ML), radon gas

Answer 396

A

measures the ability of things to mutagenize a set of strains of salmonela typhimurium

Answer 397

A

1) effect of chemical is dose dependent,
2) specific carcinogen=specific cancer,
3) time is required,
4) cell proliferation is required (rapid turnover is more risk),
5) changes transmit to daughter cells,
6) malignant risk is in stem cells,
7) malignant cells are incorrectly differentiated stem cells,
8) cancers develop through initiation and promotion

Answer 398

A

no it is the effect of a non-carcinogen.

Answer 399

A

mutagens or carcinogens. often irritants but not all irritants are promoters. often cause inflammation, Phorbol ester is best experimental example-activates kinase which activates cell proliferation

Answer 400

A

ulcerative colitis, 
atrophic gastritis, 
cholecystis, 
chosteomyelitis (may cause scams cancer), 
schistosomiasis of urinary bladder, 
chronic hepatitis

Answer 401

A

they cause mutations that accumulate in DNA! all carcinogens are mutagens, human cancers have lots of mutations, DNA repair mutations can lead to cancer, chromosomal aberrations and aneuploidy can affect/activate genes, loss of growth suppression causes

Answer 402

A

chemicals cause perterbuations in cell cell interactions and communication. carcinogens can modify protein and RNA, resulting in things like activation. many chemical carcinogens are toxic to cells, they may therefore promote improper cell growth.

Answer 403

A

lung, pancreas, colon, prostate. they are carcinomas (malignant tumors) derived from organ’s epithelium.

Answer 404

A

somewhere along the edge of the growth of the carcinoma in the epithelium, small groups of tumor cells broke through the basement membrane to invade connective tissue storm

Answer 405

A

do a biopsy! to identify as carcinoma or something else

Answer 406

A

grade and stage. both contribute to a prognosis and treatment planning

Answer 407

A

extent of tumor spread at diagnosis time. strongest predictor of prognosis. Now we use a TNM classification. T (1-4)=size of tumor, N (1-4) is lymph node involvement, M is presence of metastasis (Mo or M1)

Answer 408

A

tumor in situ

Answer 409

A

state of differentiation of tumor cells seen in histological sections. low grade-well differentiated. high grade-don’t resemble normal epithelia

Answer 410

A

squamous carcinoma= spindle shaped, produce keratin, have desmosomal connections. adenocarcinomas= form primitive glands and produce mucin.

Answer 411

A

local, distant. advanced stage=weight loss, fatigue, extreme cachexia, infection (usually acute bronchopneumonia)

Answer 412

A

present with cough, difficulty breathing, secondary pneumonia, chest pain, facial swelling, wight loss, distant mets. diagnose with imaging, biopsy, VATS (video assisted thoroscopic biopsy), cytology, meidastioscopy. 124,000 deaths from cancer from smoking each year. risk is age, duration of smoking and level, occupational history, air pollutant exposure, family history.

Answer 413

A

25-40% of cases. linked to cigarette smoking. arise from squamous metaplasia and dysplasia in bronchial tree. epithelium replaced with squamous epithelia over time. often large, necrotic, hemorrhagic near center of lesion. cancer cells are moderately-well differentiated. keratin pearls, P53 mutations, loss of Rb, p16 inactivation

Answer 414

A

25-40% of cases. most common type in women, nonsmokers. many are smokers. arise centrally. form primitive gland-like structures, positive for mucin. K-Ras mutations common. has bronchioloalveolar carcinoma (best prognosis, not linked to smoking)-cells grow along alveolar septa and airspace w/ little storm. Treat with surgery and radiation

Answer 415

A

10-15% of cases. undifferentiated high grade cancer where anapestic cancer cells may not produce keratin or mucin.

Answer 416

A

20-25% of cases. linked to smoking. arises anywhere in lung. only chemo. no differentiation. small, dark cell clusters that metastasize widely in the body. Bad news bears.

Answer 417

A

paraneoplastic. (1-5% of cases). hormones and hormone like production by cancer cells.

Answer 418

A

back pain, jaundice (due to bile duct block), cachexia, migratory thrombophlebitis. arises in all stages, mostly in cola areas of pancreatic ducts/ductules (intraepithelial neoplasias). cancer grows silently so diagnosed too late-already metastasized widely. diagnose with imaging, biopsy. treat with surgery (rare), radiation and chemo. most are differentiated adenocarcinomas. K-ras mutations. synthesize prominent connective tissue storm. Stent sometimes to prevent ascending cholangitis (leads to septic, infection, shock)

Answer 419

A

second leading cause of death in men and women. moderately well differentiated adenocarcinomas arising in mucosal layer of bowel wall. arise in pre-existing adenomatous polyps. spread via lymph/blood. 2 major types: (neoplastic colonic polyps), tubular adenoma and villous adenoma=risk for cancer. size of polyp correlates to risk. found a lot on the R side (large growths protruding into lumen), and some on L (apple core lesion, creates constipation). often metastasizes to liver. over 50, colonoscopy.

Answer 420

A

leading cause of cancer in men, second leading cause of cancer death. arise in periphery, can be felt on exam. firm mass, produce difficulties voiding urine. most common in African Americans, least common in Asians. androgens may play a role, cause is largely unknown. diagnose with ultrasound/biopsies. PSA can be elevated. progresses via loss of tumor suppressor genes. often treated by radical prostatectomy. advanced stage=anti-androgen therapy. Gleason system grading, subordinate pattern and predominant pattern are added. 8-10 is aggressive cancer.

Answer 421

A

enlarges central, peri-urethral region of gland. produces problems with voiding

Answer 422

A

drug treatment= primary treatment strategy, no surgery radiation. may be curative in some cases (germ cell cancers, Wilms tumor, etc.). used also for patients who present with advanced/metastatic disease with no other effective treatment. goal is to palliate tumor related symptoms, improve quality of life, prolong time btw. progression, improve survival

Answer 423

A

used in patients with localized cancer when localized therapies (surgery/radiation) may not be completely effective. used BEFORE surgery/radiation, can help spare vital organs (may shrink tumor to make surgery more effective, etc). may kill micrometastatic disease. goal is to increase effectiveness of the surgery/radiation, maximize tumor destruction, minimize normal tissue damage. used to treat anal, bladder, breast, esophageal, head and neck, gastric rectal cancers, osteogenic, soft tissue sarcomas

Answer 424

A

used in patients AFTER local treatment modalities (surgery/radiation). goal is to reduce incidence of localized/systemic recurrence-kill metastatic tumor cells. can increase effectiveness, improve survival rate. used to treat breast, colorectal, gastric, non small cell lung, melanoma. primary tumor removal makes it difficult to measure response to drug-relapse free survival

Answer 425

A

small. smallest in therapeutic medicine. variable pharmacokinetics mean differences in treatment with same agent (efficacy and toxicity), small changes can have large effect

Answer 426

A

UGT1A1, phase 2 enzyme is responsible for inactivating the active metabolite

Answer 427

A

more is probably better. single drugs rarely cure cancer. mutations can cause drug resistance, which makes them harder to kill with 1 drug.

Answer 428

A

drugs that are partially effective against same tumor alone should be combined! when several members of a class of drug are available, choose ones that have toxicities that don’t overlap with other agents (more side effects but less lethal interactions). use drugs in optimal doses and schedules. use intervals as short as possible. avoid removal or dose reduction from combination since this may allow resistant cells to grow

Answer 429

A

try to find a cytotoxic agent that can kill tumor cells (death via apoptosis). identify the maximally tolerated dose (MTD) and treat as close to this as possible. hope you kill all tumor cells with as few side effects as possible. choose drug based on tumor site

Answer 430

A

BCL domains are mediated by BH3. this helps to determine if cells are near or far to death threshold. mitochondria are exposed to titrated doses of BH3 peptides to make mitochondrial outer membrane permeabilization (MOMP). primed=low dose and lots of MOMP. unprimed=high dose and little to no MOMP

Answer 431

A

despite the fact that disruption of apoptosis/cell death is a hallmark of cancer, tumor cells are closer to apoptosis threshold than most normal cells. BH3 profiling measures this proximity where death will occur

Answer 432

A

pretreatment BH3 predicts a clinical response to chemo in AML. This is done by testing how easily tumors cells undergo apoptosis

Answer 433

A

kill normal cells along with tumor ones. window is small. affects dividing cells, we aren’t often targeting defect that caused the tumor

Answer 434

A

identify particular defect that cause patient’s cancer, predict what to go after. use drug that targets that/causes death or growth arrest in tumor with the defect. determine Optimal Biological Dose (OBD) for inhibiting biological target. combine agents based on understanding how they work.

Answer 435

A

reduced uptake of drug into tumor cells/increased efflux pumps. leads to MDR (multiple drug resistance). reduced apoptosis machinery. mutations alter cellular targets. repair of cellular damage. tumor stem cells regenerate. Cancer cells are unstable and evolve to resist treatment. Inactivate the drug. Some of these processes work for one drug, but a different drug may also be needed for different resistance mechanisms (single or multiple drugs).

Answer 436

A

form covalent chemical adducts and inter strand crosslinks. if they don’t repair, no replication. apoptosis

Answer 437

A

nitrogen mustard. alkylating agent. most frequently used. used for breast cancer and lymphomas, child tumors, solid tumors. inactive, must be metabolized. metabolite is ALDH substrate. cells with high levels ALDH are resistant. *think about how drug metabolized to understand how it works. *

Answer 438

A

reactions with cellular molecules. GSH tripeptide with free cysteine sulphydryl reacts with inactive alkylating agents. DNA repair removes alkyl group from guanine. cross link repair-high levels NER to remove crosslinks

Answer 439

A

hematopoeitic toxicity. dose limiting. nausea, vomiting, gonadal toxicity, alopecia, carcinogenesis. increased risk of cancer.

Answer 440

A

anti cancer drug. derivatives are less toxic. crosslink DNA making replication impossible-apoptotic response. effective testicular and ovarian, head and neck, lung, bladder cancer

Answer 441

A

reduced accumulation (decreased uptake, increased efflux), inactivation, increased NER repair, more repair proteins, increased tolerance DNA damage. inhibition of aopoptotic response.

Answer 442

A

cisplantin-nephrotoxic (aggressive hydration helpful). nausea, vomiting, ototoxicity. damage inner ear. neurotoxicity. carboplatin (myelosuppression, platelet toxic), oxliplatin (sensory neuropathy). different toxicities with different PK.

Answer 443

A

pyrimidine analogue. activates intracellular FdUMP by Thymidine kinase. (causes dTTP deletion and inhibits DNA synthesis). Inhibits DNA synthesis and activates apoptotic response because of DNA damage. GI, breast, head/neck, ovarian

Answer 444

A

target enzyme is altered. point mutations=reduced affinity FdUMP. regulation of translation, TS suppresses mRNA translation. inactivation of normal feedback TS level mechanism

Answer 445

A

primarily on rapidly growing normal cells. myelosuppression, gastrointestinal toxicitgy. alopecia, derm problems

Answer 446

A

topoisomerases help package chromatin. form temp. single/double strand breaks in DNA and religation. derived from natural products.

Answer 447

A

stabilize cleavable complex btw. topoisomerase and DNA, inhibiting relegation to leave the breaks. damage=apoptosis. used in breast, ALL, AML, lymphoma, sarcoma, other.

Answer 448

A

increased drug efflux. important for etoposide, doxorubicin. mutations confer resistance don’t alter enzyme activity

Answer 449

A

myelosuppression. can result cardiotoxicity and acute and chronic effects. associated with chelating ability, damage due to levels of ant-oxidant enzymes (catalse) lower in heart. iron chelators may protect. can cause secondary malignancies (esp. in AML)

Answer 450

A

polymers of alpha and beta tubulin. stabilizes or destabilizes microtubule dynamics to activate apoptosis

Answer 451

A

naturally occurring (vinblastine, vincristine). used pediatric malignancies, hematopoietic tumors, solid tumors. bind tubulin and cause depolymerization

Answer 452

A

increased drug efflux. MDR transporters (MDR1). cross resistance other drugs. mutations in tubulin and alter binding

Answer 453

A

neurotoxicity, damage to nerve cells (esp. wi/vincristine). myelosuppression, neutropenia

Answer 454

A

paclitaxol, docetaxel. occurring compounds from pacific yew tree bark. used breast, ovarian, lung, solid. bind interior of microtubule and stabilize against depolymerization by altering dissociation rates. blocks mitosis

Answer 455

A

drug efflux: MDR family ABC transporters. cross resistance other drugs. mutations in tubular prevent binding. inhibition apoptosis

Answer 456

A

myelosuppression-neutropenia. peripheral neuropathy. alopecia

Answer 457

A

treat hormonally responsive cancers (breast, prostate, endometrial)

Answer 458

A

estrogen receptor inhibitor

Answer 459

A

bind androgen receptor and inhibit transcription factor

Answer 460

A

catalyze synthesis of estrogen from androgens. inhibits this

Answer 461

A

inhibit testosterone production

Answer 462

A

side effects are associated altered steroid hormone signaling. hot flash, bone density change, gynecomastia

Answer 463

A

rituximab (anti CD20, B cell tumor treatment), perception (anti-her2 breast cancer), avastin (anti-VEGF colon cancer), inhibit function of target. some deliver toxins, chemotherapeutic drugs, radioisotopes

Answer 464

A

antibody recognizes antigen displayed on B cell tumors derived from progenitor cells at different stages of differentiation

Answer 465

A

targeted to defects that cause tumor development. less toxic. may be highly effective. we have few examples were they cure alone. resistance is almost always guaranteed.

Answer 466

A

caused by single oncogenic event (fusion of Bcr-Abl), translocation makes active tyrosine kinase Bcr-Abl. Imantinib inhibits the active site of the enzyme. majority of resistance is appearance of resistant alleles. Most Imatinib resistant patients have mutations that alter drug binding. Dasatinib works in CML patients with mutated Bcr-Abl (resistant to Imatinib)

Answer 467

A

CTLA-4 reduces T cell activation to maintain self-tolerance (negative signals sent in response to dendritic activation). if you block this you enhance T cell activation. PDL-1 mechanism inhibits T cell effector function, if tumors have unregulated PDL-1 they can avoid immune destruction

Answer 468

A

Adjuvant- after local treatment, trying to kill micrometastases. Neoadjuvant- before localized treatment such as surgery, trying to make that treatment more effective and less damaging. Primary- on its own with no other therapy in a few cases curative, more often for palliation of symptoms in patients with advanced disease.

Answer 469

A

Conventional agents damage normal cells as well as tumor cells- therapeutic window is largely based on tumor cells being closer to their apoptotic threshold, MTD relevant for conventional agents less so for targeted agents, which are usually less toxic, resistance mechanisms different. Remember: conventional cytotoxics hit specific targets (e.g. Topoisomerase/DNA) just like “targeted” agents do- difference is that with the newer “targeted” agents we aim to hit a target that is different/faulty in tumor cells but not normal cells.

Answer 470

A

Combine agents that work to at least some extent on their own, avoid overlapping toxicities, use drugs at optimal doses, keep treatment-free schedules as short as possible. Works because of the heterogeneity in the tumor cell population- some tumor cells respond to drug A some to drug B.

Answer 471

A

DNA damaging agents, toposiomerase interacting agents, microtubule interacting agents, hormonal agents, antibodies, kinase inhibitors. Some resistance mechanisms generally applicable- e.g. drug efflux through transporters, resistance to apoptosis.
Some resistance mechanisms specific to agent- e.g. mutations in drug target, activation of repair mechanisms, other ways to activate steroid receptors. Many drugs have similar toxicities- usually associated with damage to fast growing cells- GI toxicity, myelosuppression. Specific toxicities depend upon mechanism of action- e.g. neurotoxicity associated with microtubule-interacting agents.

Answer 472

A

small differences in drug handling can have major effects. polymorphisms can can affect toxicity and activation dramatically.

Answer 473

A

DNA damaging agents, topoisomerase interacting agents, antimetabolites, microtubule interacting agents, hormonal agents antibodies, kinase inhibitors, immune checkpont inhibitors

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Disease and Defense Unit 2-class of 2019 Flashcards

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