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Disease and Defense > Unit 2b > Flashcards

Unit 2b Flashcards

1
Q

Transudates are caused by…

A

increased hydrostatic pressure OR reduced oncotic (osmotic) pressure

vascular wall still intact

EX) heart failure, fluid overload, liver disease, venous obstruction

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2
Q

Exudates are caused by…

A

increased vascular permeability (endothelial contraction or direct damage) and inflammation

EX) Inflammation, toxins, burns

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3
Q

Transudate typically is made up of…

A
  • low proteins, low specific gravity
  • NO WBCs
  • high fluid/serum glucose ratio
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4
Q

Exudate typically is made up of…

A
  • high protein content, high specific gravity
  • low fluid/serum glucose ratio (eaten by inflammatory cells)
  • lots of WBCs!
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5
Q

Edema

A

fluid accumulation in interstitial TISSUE

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6
Q

Effusion

A

fluid accumulation on body cavity (SPACE)

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7
Q

Congestion (characteristics)

A
  • impaired blood flow to tissue/organ
  • impaired venous outflow (blood backs up into organ)
  • pathologic, passive
  • deoxygenated blood (pale or red/blue)
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8
Q

Hyperemia

A
  • increased blood flow to a tissue or organ
  • caused by arteriolar dilation
  • physiologic, active (exercise, etc. can cause this - need more nutrient rich blood to an area)
  • Oxygenated blood (red)
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9
Q

Left heart failure –> ?

A

Left heart failure →

fluid not moving out of LV

→ build up fluid in lungs (pulmonary edema, pleural effusions), low BP, low tissue perfusion

→ decreased renal blood flow → tries to fix that by holding onto fluid - retention of Na+ and H2O

→ increase blood volume → peripheral edema
→ fluid eventually builds up in right heart

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10
Q

Right heart failure –> ?

A

Right heart failure →

fluid builds up in venous system

→ liver congestion

→ backup fluid into spleen (splenic congestion), gut (GI tract varices), and ascites (fluid collection in abdomen)

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11
Q

Hemorrhage (def), and what causes it (3)

A

def: Blood outside of the vasculature due to vessel damage.
1) Impaired integrity of vessel walls (trauma, etc.)
2) Low level / function of platelets
3) Low level / function of coagulation factors

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12
Q

Petechia
Purpura
Ecchymoses
Hematoma

A

Types of hemorrhage

Petechia = 1-2 mm (small, pinpoint hemorrhage)
Often due to problem with clotting/platelets

Purpura = > 3 mm
Ecchymoses = 1-2 cm
Hematoma = large blood collection within tissue
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13
Q

Key elements of Virchow’s Triad that leads to thrombosis

A

1) Endothelial injury (hypercholesterolemia, inflammation)
2) Hypercoagulability (Inherited or acquired - cancer)
3) Abnormal Blood Flow (Stasis - bed rest, afib or Turbulence - atherosclerotic vessel narrowing)

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14
Q

Thromboemboli - venous

source
organs affected
clinical outcome

A

source = *deep leg veins, arm veins

organs affected = lungs (pulmonary embolus)

clinical outcome - respiratory insufficiency, chest pain

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15
Q

Deep vein thrombosis

A

largely due to stasis

Causes/Risks: immobility, recent surgery, estrogen, pregnancy or post-partum, previous/current cancer, coagulation abnormalities, limb trauma and/or ortho procedures, obesity

Block venous outflow

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16
Q

Atheroemboli

source
organs affected
clinical outcome

A

source: *athersclerotic plaque of aorta, iliac, carotid arteries

organs affected: legs, brain, GI tract, kidney

clinical outcome: stroke, tissue necrosis in the leg, GI pain, GI bleeding, acute kidney injury

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17
Q

Fat/Bone Marrow emboli

source
organs affected
clinical outcome

A

source: *longbone fractures –> vein damage

organs affected: lungs

clinical outcome: respiratory insufficiency 1-3 days post trauma, Altered mental status

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18
Q

Amniotic fluid emboli

source
organs affected
clinical outcome

A

source: torn placental membranes, uterine vein rupture

organs affected: lungs, brain vasculature

clinical outcome: during labor or immediately postpartum onset of respiratory insufficiency, shock, seizures, DIC

**10% of maternal deaths

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19
Q

Tumor emboli

source
organs affected
clinical outcome

A

source: Mucin-secreting adenocarcinomas, liver, kidney

organs affected: lungs

clinical outcome: espiratory insufficiency, chest pain

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20
Q

Thromboemboli - arterial

source
organs affected
clinical outcome

A

source: Heart (vegetations or mural thrombi), aorta, carotid artery

organs affected: Legs (75%) and Brain (10%)

clinical outcome: Stroke, tissue necrosis in the leg

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21
Q

Gas bubble emboli

source
organs affected
clinical outcome

A

source: Diving (nitrogen), IV, IA, or chest trauma (air)

organs affected: muscle, joints, lungs, heart

clinical outcome: Bends (skeletal and joint pain), chokes (lung edema and hemorrhage), respiratory insufficiency, myocardial ischemia

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22
Q

Disseminated Intravascular Coagulation (DIC)

A

Thrombosis and hemorrhage occur simultaneously

Generalized activation of clotting (procoagulant release - tissue factor)

→ widespread THROMBOSIS (fibrin deposition)

→ consumption of platelets and clotting factors

→ deficiency in platelets and clotting factors → BLEEDING

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23
Q

Signs/Symptoms of DIC

A

Respiratory insufficiency, MSC, Convulsions, Acute renal failure, Petechiae Purpura, GI or oral hemorrhage

Shock

Hemolytic anemia, thrombocytopenia, low fibrinogen, and elevated D-dimer and other fibrin degradation products

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24
Q

Infarction

A
  • tissue death (necrosis) caused by vessel occlusion

- Typically coagulative necrosis (liquefactive necrosis in the brain)

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25
Q

White infarction (4 characteristics)

A

Arterial insufficiency

Single blood supply

NO reperfusion

Dense tissue type (EX - heart, kidney, spleen)

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26
Q

Red infarction (4 characteristics)

A

Venous insufficiency

Dual blood supply

YES reperfusion

Loose tissue type (EX - lung, liver, intestine)

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27
Q

Shock

A

hypoperfusion of cells and tissue

Circulating blood volume or blood pressure is not adequate to perfuse body tissues → multiorgan dysfunction/damage

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28
Q

Cardiogenic Shock

A

myocardial pump failure

Myocardial damage, extrinsic compression, outflow obstruction

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29
Q

Hypovolemic shock

A

low blood volume

Severe dehydration (vomiting, diarrhea), hemorrhage, burns

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30
Q

BOTH cardiogenic shock and hypovolemic shock lead to…

A

Low cardiac output, low BP → vasoconstriction, increased HR, renal conservation of fluid

NOT sufficient → coolness and pallor of skin, tachycardia, low urine output

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31
Q

Septic Shock

A

microbial infection (bacteria, fungi) = Systemic Inflammatory Response Syndrome (SIRS)

Process: Immensely elevated inflammatory mediators → fever, DIC, ARDS widespread

1) Arterial vasodilation → hypotension, warm, flushed skin
2) Vascular leakage → hypotension, edema
3) Venous blood pooling → reduced cardiac output, increased HR

Often NOT responsive to IV fluids

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32
Q

Three types of tissues in the body and their homeostatic states

A
  1. Continuously dividing: skin, gut epithelium, hematopoietic system, constant turnover, commonly gives rise to cancer because of high frequency of division—more likely to have an error.
  2. Quiescent tissues/cells: normally little turn over, capacity for proliferation if needed

EX) hepatocytes in liver can “regrow” a liver with damage.

3.Non-dividing tissue/cells: Little to no capacity for proliferation

EX) CNS neurons are terminally differentiated

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33
Q

Hypertrophy

A

increase in cell size (no increase in cell #)

Physiologic or pathologic, may be reversible.

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34
Q

Physiologic example of hypertrophy

A

change in uterus during pregnancy–reversible

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35
Q

Pathologic example of hypertrophy

A

change in heart secondary to HTN—difficult to reverse, goal is to prevent it from worsening

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36
Q

Hyperplasia

A

increase in cell number

Physiologic or pathologic

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37
Q

Hyperplasia is associated with increased risk of ____

A

neoplasia

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38
Q

Physiologic example of hyperplasia

A

change in breast tissue during puberty and pregnancy

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39
Q

Pathologic example of hyperplasia

A

change in endometrium

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40
Q

Metaplasia

A

change from one benign, differentiated cell type to another, usually in response to injury

ALWAYS PATHOLOGIC

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41
Q

Metaplasia is associated with increased risk of _____

A

neoplasia

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42
Q

2 examples of metaplasia

A

Lining of bronchus is usually columnar epithelium with ciliated border, but changes to squamous metaplasia with smoking.

Esophagus is usually squamous, but with acid reflux changes to columnar metaplasia (Barrett esophagus)

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43
Q

Neoplasia

A

“new formation”, progressive unchecked increase in cell number, CLONAL process

Generally pathologic and irreversible

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44
Q

Benign neoplasia

A

non-invasive, non-metastatic

Cause injury largely by compression/interference in function of adjacent structures (like in the brain)

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45
Q

Pathology of benign neoplasia

A

necrosis uncommon, circumscribed/encapsulated

Microscopic: well differentiated, low rate cell turnover, cytologic uniformity (cells similar to each other), boundary maintained between tumor/adjacent tissue

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46
Q

Epithelial benign neoplasia (2)

A

adenoma

papilloma

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47
Q

mesenchymal benign neoplasia (3)

A

osteoma
chondroma
fibroma

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48
Q

Benign neoplasia clinical correlates

A

Treated by excision/surgical resection alone

  • May recur (especially if incompletely excised)
  • Generally do NOT progress to malignancy
    • ** Important exception: benign, BUT premalignant neoplasms
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49
Q

Malignant neoplasms

A

invasive, metastatic = “CANCER”

  1. Tumor progression, acquisition of more and more genetic mutations allowing angiogenesis and metastasis
  2. Cause injury by local tissue destruction and distant dissemination tissue destruction
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50
Q

Pathology of malignant neoplasms

A

necrosis common, invasive into adjacent tissue

Microscopic: variable differentiation, high rate cell turnover, cytologic pleomorphism, loss of boundary between tumor/adjacent tissue

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51
Q

Epithelial malignant neoplasms

A

Carcinoma (most common cancer)

i. Premalignant lesion, in-situ phase, invasive and metastatic, grade and stave predictive of behavior

Adenocarcinoma (carcinoma with formation of glandular structures)

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52
Q

Mesenchymal malignant neoplasms

A

Sarcoma

No pre-malignant lesion, in in-situ phase

  • Invasive and metastatic
  • Grade and stage predictive of behavior
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53
Q

Hematopoietic malignant neoplasms

A

Lymphoma (lymph node origin), leukemia (bone marrow origin)

  • Some premalignant lesion (myelodysplasia), but usually no known site of origin
  • No in-situ phase
  • N/A - invasion, metastasis
  • Grade is predictive of behavior (stage is N/A)
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54
Q

CNS malignant neoplasms

A
  • No premalignant lesion or in-situ phase
  • Invasive, BUT rarely metastatic outside of CNS
  • Grade predictive of behavior (stage is N/A)
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55
Q

Pediatric neoplasms

A

very different from adults

  • Arise in context of developing tissues/organs
  • Origin in developmental precursors
  • Tend to recapitulate developmental program of tissue of origin
  • Short latency, and early metastasis
  • Few mutations - lots of epigenetic dysregulation
  • Relative chemosensitivity (at a cost)
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56
Q

Epidemiology of cancer

A

1 in 2 americans will get cancer and 1 in 5 will die

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57
Q

Non genetic etiology of cancer (6)

A
  1. Age (accumulate more mutations as you get older)
  2. Lifestyle/environment (tobacco and EtOH use)
  3. Occupational hazards and chemical carcinogens (radium, asbestos)
  4. Radiation (UV light)
  5. Infection (viruses like HPV
  6. Inflammation (inflammatory bowel disease, ulcerative colitis)
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58
Q

Genetic AD diseases that lead to cancer (4)

A

retinoblastoma-RB, Li-Fraumeni syndrome- p53, Familial adenomatous polyposis- APC, breast/ovarian tumor-BRCA1/2

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59
Q

Genetic AR diseases that lead to cancer (2)

A

XP, ataxia telangiectasia

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60
Q

Familial cancers (3)

A

breast, pancreatic, ovarian

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61
Q

Hallmarks of cancer (3)

A
  1. Disruption of normal homeostatic mechanisms
  2. Limitless replicative potential and angiogenesis
  3. Ability to invade surrounding tissue and spread to distant sites
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62
Q

Altered cell-autonomous mechanisms

A

(activation of oncogenes, inactivation of tumor suppressors)

Ongoing genetic alterations + selection → clonal evolution

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63
Q

Altered cell-nonautonomous mechanisms

A

Altered microenvironment (surrounding tissue, stroma blood vessels, immune cells) and macroenvironment (circulating cells, factors)

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64
Q

Cancer cells express ___ and ___ to achieve limitless replicative potential and angiogenesis

A

Express telomerase - avoid normal replicative senescence

Express VEGF - promote angiogenesis

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65
Q

Dysplasia

A

“Disordered Growth”

1.Hallmark of early premalignant neoplasia in epithelia

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66
Q

Histologic features of dysplasia(3)

A
  1. Loss of cytologic uniformity
  2. Loss of normal histologic maturation
  3. Loss of architectural orientation

*** Assigned histologic grade

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67
Q

Low grade dysplasia

A

more differentiation, greater resemblance to normal

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68
Q

High grade dysplasia

A

less differentiation, less resemblance to normal

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69
Q

Tumor grade predictability

A

Can be predictive of biologic behavior (tumor dependent), but overall less reliable than disease stage

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70
Q

TNM classification

A

T= tumor: range is from Tis (in situ dysplasia or intramucosal carcinoma) to T4 (tumor invades adjacent organs or visceral peritoneum).

N=regional lymph nodes: range is from NO (no regional lymph node metastasis) to N2 (metastasis in 4+ regional lymph nodes)

M= distant metastasis: MO (no distant mets) to M1 (distant mets or seeding of abdominal organs)

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71
Q

Invasion

A

infiltration of adjacent tissue by malignant cells

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72
Q

Metastasis

A

transfer of malignant cells from the primary site to a non-connected (secondary) site

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73
Q

Malignant tumors =

A

invasion + metastasis

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74
Q

3 mechanisms of metastasis

A
  1. lymphatogenous
  2. hematogenous
  3. cavitary
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75
Q

Why is it favorable for tumor cells to undergo metastasis

A

Conditions get crowded and harsh at primary tumor site

  • selective pressure to gain ability to “move out” or metastasize
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76
Q

4 steps of tumor progression (metastatic cascade)

A
  1. Invasion
  2. Intravasation
  3. Extravasation
  4. Colonization
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77
Q

4 major theories of metastasis

A
  1. Clonal Evolution Model:
    - Mutations accumulate in genetically unstable cancer cells
    - Tumor becomes heterogenous → set of subclones develop ability to complete metastasis
    - Rare cell acquires all necessary genetic alterations to complete steps
  2. Metastasis is the result of multiple abnormalities that occur in many cells of a primary tumor - early in development of tumor = metastasis signature
  3. Background genetic variation and resulting variation in gene expression in the human population contributes to generation of metastases
    - Everything strongly impacted by background genetics
  4. Tumor microenvironment and influences like chronic inflammation effect metastasis
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78
Q

4 stages of invasion

A
  1. dissociation of cells from one another (alteration in adhesion molecules)
  2. local degradation of basement membrane and interstitial connective tissue
  3. changes in attachment of tumor cells to ECM proteins
  4. locomotion, propel tumor cells through degraded basement membranes and zones of matrix proteolysis
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79
Q

Glycoprotein that holds together epithelial cell

A

E cadherin

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80
Q

___ connects E-cadherins to actin cytoskeleton

A

B-catenin

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81
Q

Adenocarcinomas → E-cadherins ___->

A

Adenocarcinomas → E-cadherins down-regulated → facilitate detachment from primary tumor

82
Q

Epithelial to mesenchymal transition

A

normal developmental process used inappropriately by cancer cells → loss of E-cadherin expression

83
Q

MMPs regulate tumor invasion by: (2)

A
  1. Remodeling soluble components of basement membrane
  2. Releasing ECM-sequestered growth factors
    - Cleavage products of collagen and proteoglycans have chemotactic, angiogenic, and growth-promoting effects
84
Q

Ameboid migration

A

cell squeezes through spaces in cell matrix instead of cutting through it (with proteases)

  • Quicker, collagen fibers used as “high-speed railways”
85
Q

Tumor cells can switch between ___ and ___ migration

A

ameboid

MMP

86
Q

Describe the changes in attachment of tumor cells to ECM proteins

A

Receptors (integrins) for basement membrane lamin/collagens on basal surface allow epithelial cells to maintain resting differentiated state

Loss of adhesion → apoptosis (normal cells)

Tumor cells resistant to apoptosis and matrix is modified to promote invasion and metastasis

Modifications to bm

87
Q

Tumor cell modifications to basement membrane

A

cleavage of bm proteins (collagen IV and lamin) by MMP2 or MMP9 → novel sites that bind to receptors on tumor cells and stimulate migration

88
Q

Final stage of invasion process

A

Attach matrix at leading edge, detach matrix at trailing edge, and contract actin cytoskeleton to ratchet forward

89
Q

Cells and signaling factors involved in the final stage of invasion

A

a. Movement potentiated/directed by tumor cell-derived cytokines (autocrine motilite factors)
b. Collagen, lamin, and growth factors also have chemotactic activity for tumor cells - liberated by proteolytic cleavage of matrix
c. Stromal cells → produce paracrine effectors of cell motility (hepatocyte GF-scatter factor)
d. Tumor-associated Fibroblasts → can encode ECM molecules, proteases, protease inhibitors and GFs

90
Q

Intravasation

A

getting into the vasculature

91
Q

In circulation, tumor cells are vulnerable to destruction by: (3)

A
  1. Mechanical shear stress
  2. Apoptosis stimulated by loss of adhesion (anoikis)
  3. Immune defense
92
Q

How do tumor cells enhance survival in circulation? (2)

A

aggregating in clumps and with blood cells (esp platelets), activating coagulation factors (forms emboli)

93
Q

Extravasation

A

Getting out of vasculature at distant site

94
Q

Process of extravasation

A

Adhesion to endothelium → egress through basement membrane (uses adhesion molecules - integrins, lamin receptors, proteolytic enzymes)

95
Q

CD44

A

adhesion molecule, expressed on normal T-lymph

  1. Used by cancer cells to migrate to selective sites in lymphoid tissue
  2. Overexpression of CD44 favors metastatic spread
96
Q

Site of exit for circulating tumor cells

A

Site of exit for circulating tumor cells may be due to anatomic location of primary tumor

** Natural pathways of drainage do not wholly explain distribution of metastases

97
Q

Two theories of tumor colonization

A
  1. Seed and soil theory

2. Ewing’s mechanical arrest theory

98
Q

Seed and soil theory

A

Organ-specific patterns explained by needs of cancer cell (seed) for a specific environment (soil) to initiate and maintain growth

a. Extravasation requires adhesion to endothelium: tumor cells express adhesion molecules and endothelial cells of target organ and vascular beds express ligands for adhesion molecules
b. Chemokines: chemokine receptors on cancer cell and tissues that cancer cells commonly metastasize to express that chemokine

c. Some tissues are nonpermissive environment (unfavorable soil)
i. e.g. skeletal muscle

99
Q

Ewing’s mechanical arrest theory

A

cells mechanically arrest in the first capillary bed encountered

100
Q

Seed and Soil vs. Ewing’s

A

Two theories NOT mutually exclusive - cells arrest due to mechanical obstruction and chemical signals and then require suitable microenvironment for maintenance of secondary tumor growth (colonization)

101
Q

Tumor cells efficacy colonizing new regions

A

Tumor cells actually not that good at colonizing new regions

a. Dormancy = prolonged survival of micrometastases without progression
b. Tumor cells secrete cytokines, GFs, and ECM molecules that act on stromal cells → in turn make metastatic site habitable for cancer cell

102
Q

Ultimate effects of metastasis

A

Direct effect of metastases: invasive masses interfere with normal function

Indirect effect of metastases: paraneoplastic syndrome (paracrine/endocrine effects) - in 7-15% of patients with cancer

103
Q

Ultimate causes of mortality due to cancer (5)

A

i. Infection (41.6%)
ii. Organ Failure (19.2%)
iii. Hemorrhage (8.8%)
iv. Thromboembolism (12.2%)
v. Emaciation (7.7%)

104
Q

__% of malignant neoplasms are caused by environmental factors. How do we know this?

A

80%

i. Regional differences in cancer rates
ii. Worldwide differences in rates of specific types of cancers

1.Not due to genetics alone - migrants’ descendants adopt cancer risk of country to which they move and lose risk from where they’ve come

105
Q

Top 3 leading causes of death from cancer in males

A

lung cancer (34% of cancer deaths), then prostate (12% of deaths) and colon/rectum (11%)

106
Q

Top 3 cancers with highest incidence in men

A

prostate, lung, then colorectal

107
Q

Top 3 leading causes of death from cancer in females

A

lung (21% of deaths), breast (18%), colon/rectum (13%)

108
Q

Top 3 cancers with highest incidences in women

A

breast, lung/bronchus, and then colon/rectum

109
Q

___% of all cancer deaths due to tobacco

A

30%

110
Q

Top 4 environmental carcinogen classes

A
  1. polycyclic aromatic hydrocarbons
  2. Aromatic amines
  3. Nitrosamines and nitrosamides
  4. Aflatoxin

*** often “activated chemicals

111
Q

Polycyclic aromatic hydrocarbons

A

EX:(benzo(a)pyrene)
from incomplete combustion of fossil fuels

1.Ultimate carcinogen is the diol, epoxide

112
Q

Aromatic amines

A
  • Industrial and consumer products

- N-hydroxylation and sulfation are required

113
Q

Nitrosamines

A
  • formed when 2-amines in food react with nitrous acid in stomach
  • Microsomal hydroxylation leads to carbonium intermediate
114
Q

Aflatoxin

A

common in moldy grains and ground nuts (especially in tropics/developing nations)

  1. In US most exposure comes from moldy corn and wheat
  2. Produced by Aspergillus flavus
  3. Microsomal epoxidation is required
115
Q

chemical carcinogen differ in structure but are similar how?

A

Must be “Activated: Chemical carcinogen metabolized by microsomal enzymes (CYP450) → chemically active form

116
Q

Active metabolite of carcinogens

A

strong electrophile, can chemically modify protein, RNA and DNA → bases modified or “bulky” adducts → no excision/repair then mutations occur (mispairing or frameshift)

117
Q

Direct acting carcinogens

A

Not all carcinogenic compounds require activation - some are direct acting

  1. Alkylating agents
  2. Acylating agents
118
Q

Ames Test

A

Measures ability of given chemical to “mutagenize” a set of specific strains of the bacterium Salmonella (in presence of CYP450)

Process: Load onto plate without histidine, plus 10^8 His (-) bacteria, and liver enzymes (CYP450)- mutagenized bacteria able to grow without histidine

  1. → 90% of carcinogens tested are mutagens in Ames test →proves they produce mutations in our DNA
  2. Potency of mutagens parallels their carcinogenicity
    - Fast, inexpensive, sensitive
119
Q

Principles of carcinogenesis (8)

A

i. The effect of a chemical is dose-dependent in causing cancer
ii. Specific carcinogen often causes one specific type of cancer
iii. Carcinogenesis requires time (lag from exposure → cancer)
iv. Carcinogenesis requires cell proliferation
v. Cellular changes that trigger carcinogenesis are stably transmitted to daughter cells
vi. The cell at risk for becoming malignant is the stem (or reserve cell)
vii. Malignant cells are stem cells that fail to differentiate normally
viii. Cancers develop through two distinct stages

120
Q

Tissues at greatest risk of carcinogenesis

A

ones that are continually proliferating

121
Q

Two distinct stages of cancer development

A

Stage 1: Initiation - direct effect of carcinogen, mutation (irreversible)

Stage 2: Promotion - effect of a non carcinogen (reversible), requires repeated application following initiation

122
Q

Tumor promoter

A

Not mutagen or carcinogen

Often irritants, but not all irritants are promoters

Often cause inflammation (produces ROS → mutagenic, promotes cell proliferation → decreases chance mutation is fixed)

   EX) Ulcerative colitis, cholecystitis, atrophic gastritis, chosteomyelitas, schistosomiasis, chronic hepatitis
123
Q

EX of tumor promoter

A

Phorbol ester - competitively inhibits binding of diacylglycerol to protein kinase C → sustained activation of kinase → promotes cell proliferation

124
Q

Why are cancers common in elderly?

A

Takes time to accumulate mutations - some theories that it is associated with decline in immune system function

125
Q

Pathology of benign tumor (3)

A

i. NOT malignant, never invades nor metastasizes
ii. Grow slowly, encapsulated by thin rim of CT
iii. Dangerous in a confined space, and can overproduce harmful proteins

126
Q

Histology of benign tumor (3)

A

uniform appearance, less differentiated than normal epithelial cells (still resemble normal epithelial cells), low mitotic activity

127
Q

Pathology of malignant tumor

A

i. Invasion: tumor cells break through basement membrane that separates epithelium from underlying submucosal and CT stroma → invades CT stroma
ii. Metastasis: emigrating tumor cells access lymphatic and venous tributaries through sub mucosa
1. Can also directly shed and seed body cavities without breaking through the basement membrane

128
Q

Histological feature associate with “invasion”

A

Breaking of basement membrane

129
Q

Tumor grade

A

state of differentiation of tumor cells seen in histological sections

  1. Low grade = cells well differentiated, feature of normal cells
  2. High grade = cells do not resemble “normal” epithelial cells
    a. Pleomorphic, anaplastic (lack differentiation), high N:C ratio, unusual mitotic figures, high mitotic rate
130
Q

Tumor stage

A

extent of tumor spread at time of diagnosis

  • Strongest predictor of prognosis
  • Advanced stage = large tumor primary, positive nodes, and distant metastasis
  • Determined with TNM classification
131
Q

Risk factors for lung cancer (5)

A

Smoking (duration and level), age, occupational history, exposure to air pollutants, family history

132
Q

Four major types of lung carcinoma

A
  1. squamous
  2. adenocarcinoma
  3. large cell
  4. small cell
133
Q

Clinical presentation of lung carcinoma

A

cough (or change in cough), dyspnea, secondary pneumonia, CP, persistent hoarseness, facial swelling, weight loss, signs of distant mets

134
Q

4 characteristics of lung carcinoma

A
  1. Survival strongly correlated with stage
  2. Cure requires complete surgical excision of cancer
  3. Peak incidence at age 70
  4. Risk: smoking (pack:years) - 10% of heavy smokers develop lung cancer
135
Q

Squamous carcinoma is linked to

A

cigarette smoking

136
Q

Changes that occur in squamous carcinoma

A

Pseudostratified ciliated columnar epithelial cells replaced by squamous epithelium (metaplasia)

1.Arise from areas of squamous metaplasia and dysplasia (centrally, usually in major bronchi)

137
Q

Histology of squamous carcinoma

A

Large, necrotic, moderately differentiated, stain + for keratin

138
Q

Common molecular signatures of squamous carcinoma

A

P53 mutation, loss of RB/p16 are common molecular signatures

139
Q

Squamous carcinomas spread via

A

lymphatics or blood

140
Q

Treatment of squamous carcinoma

A

aurgery and radiation

141
Q

Adenocarcinoma is the most common type of lung cancer in __ and ___

A

women and nonsmokers

-“least bad” of the lung cancers

142
Q

Location of lung adenocarcinomas

A

central or periphery

- “scar carcinoma” in areas of previous scarring

143
Q

Adenocarcinomas form

A

primitive gland like structures

144
Q

Adenocarcinomas stain positive for

A

mucin

145
Q

Common mutation in adenocarcinomas

A

k- ras

146
Q

Treatment of lung adenocarcinomas

A

Surgery and radiation

147
Q

Bronchioalveolar carcinoma

A

subclass of adenocarcinoma, not linked to smoking, best prognosis

-LEAST linked to smoking

From alveolar septae along airspace structures, little stroma

148
Q

Large Cell carcinoma

A

(10-15% of cases)

  1. Undifferentiated, high grade, lung cancer, very aggressive
  2. Arise from anywhere in the lung
  3. ANAPLASTIC appearing cancer cells, very pleomorphic in appearance
    a. No keratin or mucin
149
Q

Small cell carcinoma link

A

Strong link to cigarette smoking

150
Q

Small cell carcinoma

A

arise from anywhere in lung

151
Q

small cell carcinoma treatment

A

not treated with surgery, only chemo

152
Q

Histology small cell carcinoma

A

small, dark staining, form cluster

153
Q

Small cell carcinomas stain + for

A

neuroendocrine markers

154
Q

Prognosis of small cell carcinoma

A

terrible

155
Q

Clinical presentation pancreatic carcinoma

A

back pain, unexplained jaundice (cancer growth blocks common bile duct), cachexia, migratory thrombophlebitis

1.Terrible 5 year survival (

156
Q

Risk factors of pancreatic cancer

A

largely unknown

age, smoking, chronic pancreatitis from alcoholism, DM, family hx

157
Q

Pathology of pancreatic carcinomas

A
  1. Arise in major ducts, not acini (focal areas of non-invasive epithelial cell proliferations)
  2. Well differentiated adenocarcinomas
  3. Desmoplasia
158
Q

Desmoplasia

A

synthesis of prominent CT stroma → rock hard feeling

159
Q

Prognosis of pancreatic carcinoma

A

terrible prognosis (worse than lung cancer)

  1. Silent cancer growth without symptoms or signs - wide metastases at time of diagnosis (mets to liver, abdominal nodes, celiac nerve plexus)
  2. Best case = small tumor found at head of pancreas
160
Q

Treatment of pancreatic cancer

A
  1. Non-resectable usually → radiation + chemo treatment

2. Surgery = Whipple

161
Q

98% of colorectal carcinomas are ___

A

adenocarcinomas

162
Q

Pathology of colorectal carcinomas

A
  1. Moderately well differentiated adenocarcinomas - arise in innermost mucosal layer of bowel wall
    a. Mucosa → then can invade submucosa and muscularis layers
  2. Sporadic - arise in preexisting adenomatous polyps
  3. often metastasize to the liver
163
Q

Two types of neoplastic colonic polyps

A
  1. tubular adenoma

2. villious adenoma

164
Q

Spread of colorectal cancer

A

lymphatics or blood

165
Q

Symptoms of colorectal cancer

A

Symptoms depend on if cancer is in left or right (descending) colon

Left → constipation, change in stool caliber, colon obstructed

Right → very big before producing symptoms, abdominal pain, mucus or blood in stool, anemia (due to subclinical colonic bleeding)

166
Q

Germline mutations of colorectal cancer (4)

A
  1. Rare Familial Adenomatous Polyposis (APC)
  2. HNPCC - loss of mismatch DNA repair
  3. Loss of mutY base excision DNA repair enzyme
  4. Somatic mutations = sporadic mutations in APC, K-ras, p53, DCC, MCC
167
Q

Gleason grading of prostate cancer

A

looks at morphologic resemblance to normal prostate and degree of invasiveness

168
Q

Grade 1 of gleason

A

very well differentiated, neoplastic glands uniform

169
Q

Grade 5 of Gleason

A

no gland formation, tumor cells infiltrate as sheets and cords

a.Highest grade

170
Q

How do you get the final Gleason score?

A

Add Gleason grade of subordinate pattern and predominant pattern

a. Values of 8-10 = aggressive behavior

171
Q

Clinical presentation of prostate cancer (3)

A
  1. Enlarged prostate (not always though)
  2. Difficulty with urinary voiding
  3. Typically occurs in periphery of gland
172
Q

Risk factors of prostate cancer

A

age (rare before 40, common by 80), race (most in African-Americans, least in Asians), geography, family hx (genetics)

173
Q

Death in prostate cancer

A

Most men die with Pca but not of it

174
Q

Screening methods of prostate cancer (3)

A
  1. Digital rectal exam
  2. Digital guided biopsies through the rectum
  3. Prostate specific proteolytic enzyme in serum (PSA >4 ng/ml)
175
Q

Treatment of prostate cancer

A

radical prostatectomy, with/without radiation, anti-androgen therapy-

176
Q

Adjuvant chemotherapy

A

Local Therapies first (Surgery/radiation) then chemo

Can increase effectiveness of surgery/radiation and improve overall survival and increased relapse free survival

177
Q

Neoadjuvant Chemotherapy

A

Chemo first, then local therapies (surgery/radiation)

Used before surgery/radiation to spare vital normal organs

May also kill micrometastatic disease

178
Q

Primary induction chemotherapy

A

Drug treatment is primary treatment strategy (no surgery or radiation)

Often used for advanced tumor/metastatic disease patients for which no effective other treatment exists

179
Q

Conventional Cytotoxics

A
  • damage normal cells and tumor cells

- small therapeutic window (try to kill tumor cells without killing normal cells)

180
Q

Both conventional and targeted therapies attempt to…

A

Hit specific targets (e.g. topoisomerase/DNA) that interfere with fundamental aspects of cell biology

181
Q

Targeted therapies differ in that they…

A

hit target that is different/faulty in tumor cells, but not normal cells

  • MTD less relevant for targeted therapy (less toxic)
  • widens therapeutic window
182
Q

Key points for combining anti-tumor agents (5)

A

1) Combine agents that work at least some extent on their own
2) Avoid overlapping toxicities
3) Use drugs at optimal doses
4) Keep treatment-free schedules as short as possible
5) Avoid removal or dose reduction of drug (could result in outgrowth/resistant cell line)

183
Q

Main mechanisms of chemo-resistance (5)

A

1) Enhance drug efflux out of cancer cell
2) Enhance inactivation of drug
3) Alter drug target
4) Generate adaptive responses
5) Make apoptosis dysfunctional

can be specific to drug or more general resistance

184
Q

DNA modifying agents typically develop resistance by…(6)

A

1) Up-regulating DNA repair mechanisms
2) Inactivating drug
3) Resistance of apoptosis
4) increased drug efflux
5) mutation in drug target enzyme
6) increase amount of target enzyme present

185
Q

Antimicrotubule drugs

A

Target cytoskeleton (stabilize or de-polymerize microtubules)

Specifically this class of drug can be neuro-toxic

186
Q

Hormonal agents resistance mechanisms

A

Activate receptor by other mechanisms (without hormone)
Mutate receptor to alter response to drug

EX) Tamoxifen, anti-androgens

187
Q

Antibody therapies can work by…

A

binding target molecule and inhibiting function of molecule

-Can also be used as immunoconjugates to deliver toxins / chemotherapeutic drugs to tumor cells specifically - inhibit function and kill cell!

188
Q

Kinase inhibitors typically work by…

A

binding directly to active site of kinase enzyme where ATP binds

EX) Imatinib - treats CML/GIST

189
Q

Typical toxicities

A
  • GI toxicity
  • Myelosuppression (suppress hematopoiesis)
  • Neurotoxicity (antimicrotubule agents)
  • Cause secondary malignancies
  • Damage to fast growing cells
190
Q

Fludrocortisone

A

high MC activity, very high salt retaining side effects (oral only)

191
Q

Alkylating agents mechanism of action

A

cross link DNA, prevents DNA replication

192
Q

Cyclophosphamide is a chemo drug that is an __________.

A

alkylating agent

193
Q

Cisplatin is ________

A

an alkylating agent (chemo drug) (platinum compound)

194
Q

Carboplatin and Oxaliplatin are ___________

A

alkylating agents (platinum compounds)

195
Q

Methotrexates is ________.

Mechanism of action?

A

an anti-metabolite

reversible, competitive inhibitor of DHFR in synthesis of nucleotides

196
Q

5-fluorouracil is ________

mechanism of action?

A

an anti-metabolite

pyrimidine analog - inhibits DNA synthesis

197
Q

anti-Topoisomerase drugs act by…

A

causing DNA strand breaks

198
Q

Doxorubicin and etoposide are _____________

A

anti-Topoisomerase drugs

199
Q

Vinblastine and vincristine (aka vinca alkaloids) are ___________

A

anti-microtubule agents

200
Q

Paclitaxol and Docetaxel (aka Taxanes) are _____________

A

anti-microtubule agents

201
Q

anything ending in mab = _______

EX) Rituximab, trastuzumab/Herceptin, Bevacizumab/Avastin

A

antibody chemo agent

202
Q

Imatinib/Gleevec are ____________

A

kinase inhibitors

Disease and Defense (11 decks)

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