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Flashcards in Unit 2 Exam Deck (65):

What are the three types of malignant neoplasms?

1. Lymphoma comes from white cells
2. Sarcoma come from stroma
3. Carcinoma come from epithelia


Metaplasia vs. Dysplasia vs. Neoplasia

-Metaplasia = conversion in cell type
-Dysplasia = change in cell or tissue phenotype
-Neoplasia = irreversible abnormal proliferation
Progression: Metaplasia > Dysplasia > Neoplasia


Hypertrophy vs Hyperplasia

-Hypertrophy = increase in cell size
-Hyperplasia = increase in cell number


What are the types of reversible cell injury?

-Cellular swelling: disruption in ionic and fluid homeostasis
-Fatty changes: accumulation of lipid vacuoles within the cytoplasm of cells
-Other intracellular associated changes: 1) plasma membrane alterations (like blunting, distortion of microvilli, etc.), 2) mitochondrial changes (like swelling), 3) dilation of the ER with detachment of ribosomes and dissociation of polyribosomes, and 4) Nuclear alterations with clumping of chromatin.


What are the types of irreversible cell injury?

-Necrosis: often due to hypoxia. Almost always a pathological. Involves cell swelling, disruption of plasma membrane, bursting of cellular contents, and adjacent inflammation.
-Apoptosis: programmed cell death. Physiological. Reduced cell size, fragmentation of nucleus, intact plasma membrane, and no adjacent inflammation.
-Autophagy: process in which cell eats its own contents. An adaptive response to starvation. Implicated in some diseases.


Intrinsic vs Extrinsic Apoptosis

-Intrinsic: the mitochondrial pathway involves BCL2, BCL-XL, BAX, and BAK
-Extrinsic pathway: cytotoxic T-cells bind to surface receptors (Fas/CD95) and tell cell to die


What are the 5 types of necrosis?

1. Coagulative Necrosis
2. Liquefactive Necrosis
3. Caseous Necrosis
4. Fat Necrosis
5. Fibrinoid Necrosis


Coagulative Necrosis

Tissue architecture preserved for at least several days. Dead cells remain pale and "ghost-like." Characteristic of infarcts which are classically seen in heart following myocardial infarction, but can be seen in any solid organ following ischemia.


Liquefactive Necrosis

Seen in focal bacterial or occasional fungal infections. Microbes stimulate the accumulation of inflammatory cells and leukocyte enzymes digest the tissue. Also seen in hypoxia in CNS.


Caseous Necorsis

Necrosis characteristic of tuberculosis infection. "Caseous" derived from the white appearance of the area of necrosis. Microscopically the necrotic area appears as a collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border (granulomatous inflammation).


Fat Necrosis

Fat destruction, typically resulting from release of activated pancreatic lipase (following acute pancreatitis or trauma). Fats hydrolyzed into free fatty acids which precipitate with calcium to produce a chalky gray material.


Fibrinoid Necrosis

Immune reaction in which complexes of antigens and antibodies are deposited in the walls of arteries. Deposited immune complexes combine with fibrin and produce bright pink and amorphous appearance on H&E. Seen in certain vasculitis.


What are the 5 major mechanisms of cell injury?

1. ATP depletion
2. Mitochondrial damage
3. DNA damage
4. Influx of Calcium
5. Accumulation of Reactive Oxygen Species


Describe ATP Depletion as a mechanism of cellular injury.

ATP produced via oxidative phosphorylation of ADP in mitochondria OR glycolytic pathway in absence of oxygen. Tissues with greater glycolytic capacity better able to withstand ischemic injury. Neurons can only last 3-5 min, cardiac myocytes last 30 min to an hour, and soft tissues and skeletal muscle cells can last many hours without ATP.


Describe mitochondrial damage as a mechanism of cellular injury.

leads to failure of oxidative phosphorylation which causes ATP depletion, formation of reactive oxygen species, formation of high-conductance channel (mitochondrial permeability transition pore) and loss of membrane potential, and release of proteins that activate APOPTOSIS.


Describe the influx of calcium as a mechanism of cellular injury.

Ordinarily substantial calcium gradient between extracellular and intracellular calcium. Ischemia and toxins cause release of Ca2+ from intracellular stores and increased influx across plasma membrane.


Describe the accumulation of reactive oxygen species as a mechanism of cellular injury.

Cell injury involves damage by free radicals. Can occur in two different ways - 1) all cells during redox reactions during mitochondrial respiration or 2) phagocytic leukocytes give them off as mechanism for host defense.


Edema vs Effusion

-Edema: fluid accumulation in interstitial tissue.
-Effusion: fluid accumulation in body cavity (spaces).


Hyperemia vs Congestion

-Hyperemia: dilate arterioles to increase oxygenated blood flow to the area/capillaries. Usually physiologic. May be due to inflammatory response or during exercise.
-Congestion: impaired venous flow which causes a passive buildup of fluid in the capillaries that is deoxygenated blood. This can cause edema and tissue damage = pathologic.


Exudate vs Transudate

-Transudate: "translucent." Has low protein and WBC content. Happens when vessel wall is still intact. Happens with increased hydrostatic pressure and reduced oncotic pressure.
-Exudate: "exiting contents." Has high protein and WBC content. Happens when vessel wall is damaged or has holes in it (increased vascular permeability). Often seen with inflammation, toxins, and burns.



abnormal (often too much) clotting


Virchow's Triad of Thrombosis

1. Endothelial injury (hypercholesterolemia, inflammation)
2. Abnormal blood flow (stasis from bed rest, turbulence from athlerosclerotic vessel narrowing)
3. Hypercoagulability (factor V, disseminated cancer)



-Most common type of embolus
-Most commonly venous from DVT in legs or arms. It effects the lungs and causes respiratory insufficiency.
-Can also be arterial and come from the heart, aorta, or carotid artery. Effects the legs and brain most commonly.



-caused by atherosclerosis or aorta, iliac, or carotid arteries
-lodges in legs, brain, GI tract or kidney
-can cause stroke, tissue necrosis of leg, GI pain/bleeding, and acute kidney injury


What is disseminated intravascular coagulation?

Disseminated intravascular coagulation (DIC) is basically when you get so much clotting systemically that you actually use up all of your platelets, fibrin, and clotting factors at the same time so you end up hemorrhaging.
-When thrombosis and hemorrhage occur simultaneously
-Effects multiple organ systems and can result in shock
-One cause is an Amniotic Fluid Embolus in pregnant women


Red vs White Infarcts

-White Infarct: due to insufficient arterial supply. Seen in the heart, kidney, and spleen which only have one blood supply and cannot be reperfused.
-Red Infarct: due to venous insufficiency. Seen in the lung, liver, and intestines which have multiple blood supplies and can be reperfused.


What is shock?

circulating blood volume or blood pressure is not adequate to perfuse the body tissues which leads to multiorgan dysfunction/damage


What are 5 causes of shock?

-Cardiogenic Shock: due to myocardial pump failure. Leads to myocardial damage, extrinsic compression, or outflow obstruction.
-Hypovolemic Shock: due to low blood volume. Leads to severe dehydration (vomiting, diarrhea), hemorrhage, burns
-Septic Shock: caused by inflammatory response to microbial infection
-Anaphylactic Shock: due to allergic reaction. Caused by arterial vasodilation and vascular leakage.
-Neurogenic Shock: loss of vascular tone. Can be caused by anesthesia or a spinal cord injury.


Histological Grade vs. Stage

-Grade = degree of variation of cells
---Low grade = more differentiation/greater resemblance to normal.
---High grade = less differentiation/resemblance to normal.
-Stage = spread and size of cells


Benign vs Malignant Neoplasms

-Benign Neoplasms: does not invade or metastasize. circumscribed/encapsulated. minimal surrounding tissue damage. low rate of mitosis. well differentiated.
-Malignant Neoplasms: invades and metastasizes. cause tissue damage. less differentiated. high rate of mitosis.


What are 3 routes of metastasis?

1) Direct seeding of body cavities or surfaces (come off of site of origin, float around, and then land on secondary surface)
2) Lymphatic spread (go through basement membrane and use lymph to spread)
3) Hematogenous Spread (go through basement membrane and use blood to spread)


What are the steps of metastasis?

1. Invasion
i. dissociation of cells from one another by loss of E-cadherin and Beta-catenin
ii. local degredation of the basement membrane and interstitial connective tissue by proteolytic enzymes
iii. changes in the attachment of tumor cells to ECM
iv. locomotion of the tumor cells through the basement membrane
2. Intravasation - getting into the vasculature; tumor cells tend to aggregate with each other or other blood cells to increase their survival
3. Extravasation - getting out of the vasculature; use CD44 adhesion molecule to get out of circulation
4. Colonization - tumor cells find a favorable environment with adhesion molecules that allow them to bind and begin dividing again


Paraneoplastic Syndrome

indirect effect of metastasis where you have disease/symptoms due to cancer in the body, but not due to cancer cells directly. Examples: ecotopic hormone production (vasopressin or ADH causes electrolyte imbalance)


What are the three most common cancers diagnosed in men and women?

-Men: prostate > lung/bronchus > colon/rectum
-Women: breast > lung/bronchus > colon/rectum


Which cancers cause the most deaths among men and women each year?

-Men: lung/bronchus > colon/rectum > prostate
-Women: lung/bronchus > breast > colon/rectum
-Leukemia is in the top 5 as well


What are the two types of lung cancer and their subtypes?

1. Non-Small Cell Lung Cancer
i. Adenocarcinoma
ii. Squamous Cell Carcinoma
iii. Large Cell Carcinoma
2. Small Cell Lung Cancer (seen in smokers)


What are two hereditary types of colorectal cancer?

1. Familial Adenomatous Polyposis (FAP)
-autosomal dominant
-100% have adenocarcinoma by age 30
2. Hereditary Non-Polyposis Colorectal Cancer aka Lynch Syndrome
-autosomal recessive
-need second hit from environment to develop cancer


Left Congestive Heart Failure

-Causes: ischemic cardiomyopathy, nonischemic cardiomyopathy, hypertension, and valve disease
-Hypertrophy of left ventricle
-The blood fails to pump leads to blood getting backed up into the lungs
-Increased number of macrophages in lung cleaning up blood products


Right Congestive Heart Failure

-Causes: left heart failure, congenital heart disease, pulmonary causes (COPD, PE, tumor in lung vessel)
-Hypertrophy of right ventricle
-The blood fails to pump leading to blood getting backed up into the liver and spleen
-Will see nutmeg appearance of patient's liver indictive of congestion
-Will also see red blood cells closer to the central vein instead of the portal triad in the liver
-Can also see some hepatocytes that will lack a nucleus - indicative of necrosis
-May also see splenomegaly if it is really bad


What are the 5 manners of death to pick from on a Certificate of Death form?

i. Suicide
ii. Homicide
iii. Accident
iv. Undetermined
v. Natural


Adjuvant vs. Neoadjuvant vs. Primary Chemotherapy

-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.


Difference between conventional cytotoxics and targeted therapies in cancer treatment.

-Conventional cytotoxic agents go after targets (e.g DNA) that are equally important in normal and cancer cells. Drugs are chosen largely by location of cancer. Goal is to kill cancer cells while minimizing side effects.
-Newer “targeted” agents are designed to go after targets that are different or especially important in cancer cells. Drugs are chosen based on known defect.


What is the basis for combining anti-tumor agents?

Going after different subpopulations of cells in a heterogeneous tumor. Trying to maximize tumor killing ability while limiting toxicity to normal tissues. Want to pick drugs that have different organs that they cause toxicity in.


Why do conventional cytotoxic drugs work even though they are killing normal cells in addition to cancer cells?

-Cancer cells are usually more (not less) sensitive to apoptosis than their normal counterparts
-Despite the fact that disruption of apoptosis/cell death is a hallmark of cancer cells, tumor cells are closer to their apoptosis threshold than most normal cells. BH3 profiling can measure this proximity to the threshold where death will occur.
-The therapeutic window is narrow because you are still killing normal cells along with the cancer cells and some cell lines are more sensitive than others. For example, dividing cells in the bone marrow and GI tract are already "primed" and tend to be easy to kill.


Acute vs Chronic Inflammation

Acute Inflammation:
---innate immune system
---fast: minutes to hours
---mostly neutrophils
---results in complete resolution, abscess formation, or chronic inflammation
Chronic Inflammation:
---adaptive immune system
---slow: days
---caused by persistent infections, auto-immune system, or prolonged toxin exposure
---mostly lymphocytes and macrophages
---results in firbosis/scaring


What are the classical signs of inflammation?

-Rubor (redness)
-Calor (heat)
-Dolor (pain)
-Tumor (swelling)
-Functio Laesa (loss of function)


Describe Toll-like receptors, how they get activated, and their role in inflammation.

-Toll-like Receptors are transmembrane proteins that allow a cell to recognize microbial molecules
-Once a toll-like receptor binds to a microbial molecule extracellular, its intracellular component recruits transcriptional factors (MAP-K and NF-kB) to increase the transcription of pro-inflammatory cytokines (Pro-IL-1)
-NOD-like receptors (NLRs) are intracellular proteins that recognize a variety of substances (such as necrotic cellular debris, ion disturbances, etc). NLRs signal inflammasomes (protein complex) to activate caspase-1 (located on inflammasome).
-Activated caspase-1 cleaves Pro-IL-1 to activate it to IL-1
-IL-1 can go on to recruit WBCs and cause fever


Granulomatous Inflammation

-type of chronic inflammation where the foreign body/pathogen is encapsulated in T cells stimulated by macrophages
-common things that may cause a granuloma to form: TB, fungal infection, suture, silicosis, sarcoidosis, crohn's disease, URIC ACID CRYSTALS


Which cytokines are important in acute inflammation?

TNF, IL-1, and chemokines


Which cytokines are important in chronic inflammation?

IL-2, IL-4, IL-5, IL-17, and IFN-gamma


Which cytokines terminate the inflammatory response?

TGF-Beta and IL-10


What are the two vasoactive amines?

=mediate vasodilation and increased vascular permeability
-Histamine (mostly from mast cells)
-Serotonin (stored in platelets and neuroendocrine cells in GI tract)


What are the three mediators involved in pain?

1. Prostaglandins
2. Bradykinin
3. Substance P


What mediators cause fever?

1. IL-1, TNF
2. Prostaglandins


Aspirin's effects on COX-1/COX-2?

irreversibly inactivates COX1 and COX2


Acetaminophen's effects on COX1/COX2?

Inhibits COX2 in CNS. No effects on COX in periphery.


Traditional NSAID's effects on COX1/COX2?

Reversibly inhibit COX1 and COX2


Celecoxib's effects on COX1/COX2?

reversible inhibition of COX2



i. Therapeutic uses: Result from irreversible inhibition of COX-1 and COX-2. Low dose aspirin given to inhibit thrombus formation.
ii. Metabolism and excretion: Recall that aspirin, beyond low-dose, is a zero-order kinetic drug. This means that adding more aspirin past a certain (easily reached) point has no effect on COXs-- but it can certainly cause toxic side effects. Doesn't, as such, have a half-life. Rapidly metabolized by esterases in blood and tissues.
iii. Side effects: increased bleeding time, GI pain and nausea. Sometimes people can have aspirin hypersensitivities (as well as to other NSAIDs).
iv. Overdose: Causes tinnitis (ringing in the ears) at high concentrations. At very high concentrations, get uncoupling of oxidative phosphorylation-- metabolic acidosis, respiratory alkalosis.
v. Contraindications: No one with gastric ulcers, no chronic alcoholics. Notice that aspirin (not other NSAIDs) shouldn't be used in infants with viral infections (liver damage-Reyes syndrome). Avoid use in pregnant patients.
vi. Drug-drug interactions: Low-dose aspirin has no effect if it's taken after taking ibuprofen. Ibuprofen preferentially binds to the COXs, making aspirin incapable of binding it.



i. Therapeutic uses: mild-moderate analgesic, antipyretic. No significant anti-inflammatory effects. Considered safe at all stages of pregnancy for short-term use; weak to no effect on clotting; no GU upset; safe to give virally infected infants.
ii. Metabolism and excretion: See 'overdose,' below.
iii. Side effects: mild CNS effects; mild hepatic enzyme inducer.
iv. Overdose: recall that acetaminophen is metabolized by conjugation through easily overloaded mechanisms. It has an unconjugated, reactive intermediate form that builds up quickly in overdose situations and is extremely toxic (will destroy liver and kidney tubules). Rapid infusion of intermediate-binding molecules are needed to prevent organ failure and death. Note alcohol induces the enzyme that forms the toxic intermediate (if you've been drinking all night, don't take a bunch of Tylenol to ward off the headache you're going to have the next day).
v. Contraindications: as above.
vi. Drug-drug interactions: none noted.


Traditional NSAIDs (Ibuprofen/Naproxen/Ketorolac)

i. Therapeutic uses: Anti-inflammatory, antipyretic, analgesic. Sometimes used for arthritis. Some transient anti-clotting activity.
ii. Metabolism and excretion: rapid, complete absorption; excreted by kidney. Ketorolac is taken IV/IM; the rest can be taken po.
iii. Side effects: Less GI irritation than aspirin. Ibuprofen is the least-GI-irritating NSAID.
iv. Overdose: none noted.
v. Contraindications: Not for use in pregnant women (safety not established).
vi. Drug-drug interactions: None noted.



i. Therapeutic uses: Marketed as a COX-2 specific inhibitor. Anti-inflammatory, antipyretic, analgesic. Used for arthritis, menstrual pains, acute pain. No anticlotting effect per se.
ii. Metabolism and excretion: po admin. Metabolized by the liver, excreted by the kidney.
iii. Side effects: Some renal side effects; increased risk of adverse cardiovascular events (mainly emboli), as noted above.
iv. Overdose: No notes.
v. Contraindications: Not to be used in pregnant women (blocks uterine contractions). Note that celecoxib is a sulfonamide (sulfa drug) so watch out for allergic reactions.
vi. Drug-drug interactions: When taken with warfarin, potential for increased bleeding.


Side effects of glucocorticoids

1. Glucocorticoid Metabolic Effect
-diabetes like state, muscle wasting in extremities, centripetal obesity (moon face, buffalo hump)
2. Immunosuppression
-suppress chronic inflammation and autoimmune reactions, but also cause decrease healing and diminish immunoprotection


What are the steps of scar formation?

1. Angiogenesis
2. Migration and proliferation of fibroblasts and deposition of connective tissue (orchestrated by PDGF, FGF-2, and TGF-Beta)
3. Maturation and reorganization of the fibrous tissue to produce stable scar


What are three types of pathological scar formations?

1. Hypertrophic scar: outside boundaries of injury, regresses
2. Keloid: outside boundaries of injury, does not regress
3. Contracture: permanent muscle, tendon, or scar tissue shortening