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180 Cards in this Set
- Front
- Back
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what are the 2 main types of edema?
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1. inflammatory: due to changes in permeability
2. non-inflammatory: due to altered transcapillary hemodynamics |
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what is the term for generalized edema?
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anascara
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what is the term for edema in the thoracic cavity?
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hydrothorax
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what is the term for edema in the tissues surrounding the heart?
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hydropericardium
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what is the term for edema in the abdominal cavity?
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hydroperitoneum or ascites
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***what are the differences in fluid composition of inflammatory versus non-inflammatory edema?
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- inflammatory: an exudate with a high specific gravity (>1.020) due to high protein content
- non-inflammatory: a transudate with a lower specific gravity (<1.012) due to ultrafiltration |
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in edema, what are the pathogenic factors that lead to accumulation/retention of fluid in the tissues?
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- intravascular hydrostatic pressure drives fluid out
- colloid oncotic pressure of plasma proteins holds fluid in |
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what is the driving force for fluid motion in edematous tissue?
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the intravascular pressure at the arteriolar end is higher than the venous end, creating a pressure gradient to return blood through the venous end.
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by what two pathways does fluid from interstitium return to the blood?
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- high oncotic pressure in the capillaries facilitates return from thin-walled capillaries
- lymphatics |
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what are the four major pathological conditions that cause edema?
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1. increased intravascular hydrostatic pressure
2. fall in plasma oncotic pressure 3. impairment of lymphatic drainage/flow 4. retention of salt and water |
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what are three conditions that can lead to increased intravascular hydrostatic pressure and things that can cause them.
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1. imparied venous flow - e.g. obstructive thrombosis
2. increased venous pressure due to congestive heart failure 3. altered circulating volume - e.g. fluid rention in cardiac and renal failure; renin-angiotension-aldosterone |
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what are two conditions that can lead to reduced plasma oncotic pressure and things that can cause them.
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1. loss of albumins and other proteins: e.g. renal-proteinuria and nephrotic syndrome; GI-protein losing enteropathy
2. reduced synthesis of plasma proteins: e.g. malnutirition; cirrhosis |
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what is Johne's disease and what are its pathological signs?
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- a mycobacterial infection of the GI tract that produces granulomatous inflammation
- inflammation causes malabsorption of protein and edema |
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what are three conditions that can lead to lymphatic obstruction and things that can cause them.
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1. localized inflammatory or neoplastic lesions
2. parasitic damage to vessels 3. neoplasms and lesions induced by the treatment of neoplasms (e.g. surgery, irradiation) |
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what is the pathway for edema caused by sodium and water retention that is initiated by reduced renal perfusion?
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> reduced renal perfusion -> signal to produce more perfusion (secretion of renin) -> conversion to active angiotensin (vasopressor effects) + secretion of aldosterone (increased sodium retention/water retention -> enhanced systemic fluid level + vasoconstriction
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how do steroids affect edema?
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SSS - "steroids save sodium"; steroids such as aldosterone increase fluid retention by retaining sodium, which can lead to edema.
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increased blood in a tissue
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hyperemia
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what are the two types of hyperemia and what physiological mechanisms cause them?
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1. active hyperemia: increased arterial/arteriolar blood flow and opening of capillaries
2. passive hyperemia - aka congestion - pooling of blood in tissue and vasculature due to decreased venous drainage |
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what are three common causes of active hyperemia?
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1. acute inflammation/action of inflammatory mediators
2. demand for heat dissipation - exercise and fever 3. neurologic triggers (e.g. blushing) - affected area is usually red in color |
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what are three common causes of passive hyperemia (congestion)?
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1. congestive heart failure
2. edematous occulsion of venous drainage 3. abnormal distribution of blood (e.g. cirrhosis and portal hypertension) |
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grossly, what is a common appearance of congested tissue and what is the term used to describe this appearance?
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- it may appear red/blue/purple
- called cyanotic |
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what is the appearance of and pathway to generate chronic congestive lesions in the lung, liver, or spleen?
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- stasis of blood leads to chronic hypoxia
- this leads to degeneration/death of cells and rupture of blood vessels - old hemorrhage may be present as hemosiderin-laden scars |
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what is the primary cause and associated morphological changes associated with pulmonary congestion and edema?
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- primary cause is elevated left atrial pressure and pulmonary venous pressure
- congested capillaries and hemorrhage - phagocytosis of RBC debris in macrophages (hemosiderin-laden 'heart failure' cells) - edema and septal thickening and fibrosis |
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what is the primary cause and associated morpholoical changes associated with chronic passive hepatic congestion?
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- primary cause is elevated right atrial and vena cava/hepatic vein pressure
- 'nutmeg liver' - congestion of central vein, surrounded by zone of uncongested liver cells - atrophy of centrilobular hepatocytes caused by hypoxia and loss of nutrient exchange - fatty change/fibrosis |
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what is a petechial hemorrhage?
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minute pinpoint hemorrhages in skin, mucous membranes, or serosal surfaces, usually caused by capillary damage
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what is purpura
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a slightly larger site (about 1 cm) of hemorrhage
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what is ecchymosis?
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a big hemorrhage, like a bruise. Larger than a pruprua.
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what are the differences between hemostasis and thrombosis
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- hemostasis is a normal process; thrombosis is pathological
- hemostasis allows formation and resolution of clots; thrombosis is the formation of clots in the uninterrupted vascular system - hemostasis occurs at sites of vascular interruption; thrombosis works in the same way, but at the wrong time/site |
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what are three important physical components of hemostasis/thrombosis?
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1. vascular wall (entothelium, CT, ECM)
2. platelets 3. coagulation factors from the plasma |
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where are platelets made?
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from megakaryocytes in the bone marrow
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where are coagulation factors made and stored?
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made in the liver, stored in the plasma
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what are the five basic steps in normal hemostasis?
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1. damage to blood vessels leads to brief vasoconstriction
2. exposure of collagenous vessel valls causes adhesion and activation of platelets, which change shape and release mediators. This recruits more platelets to temporarily plug the hole. PRIMARY HEMOSTASIS 3. the release of tissue factors causes the release of thrombin, which polymerizes fibrinogen to fibrin at the clot site. SECONDARY HEMOSTASIS 4. Polymerized fibrin and platlets bind together to form a clot 5. clot is removed during healing |
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what is primary hemostasis?
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attachement of platelets at the site of vascular damage to plug the hole
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what is secondary hemostasis?
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the polymerization of fibrinogen by thrombin to form a fibrin scaffold around platelets, forming a clot.
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how do intact (uninjured) endothelial cells differ from damaged/activated endothelial cells in regulating hemostasis?
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- Intact endothelial cells have anticoagulant, antiplatlet, and profibrinolytic properties
- damaged/activated endothelial cells have procoagulant functions |
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what are four major things that activate endothelium to promote hemostasis?
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- infectious agents (e.g. LPS from G- bacteria) and metabolites
- hemodynamic factors - plasma constituents (lipids) - cytokines from leukocytes (IL-1, TNF) |
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healthy vascular endothelium produces antithrombotic effects by what three major mechanisms?
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1. antiplatelet effects
2. anticoagulant properties 3. fibrinolytic capability |
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How does healthy vascular endothelium exert antiplatelet effects?
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- prevent platelets from reaching subendothelium matrix (which would activate them when they contact collagen)
- prevent platlet adhesion - cells produce NO and prostacyclin, which inhibit platelet aggregation and vasodilate |
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How does healthy vascular endothelium exert anticoagulant properties?
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- heparin-like molecules on the plasma membrane activate antithrombin enzymes
- cells produce thrombomodulin, which binds and cleaves thrombin |
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How does healthy vascular endothelium exert fibrinolysis?
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- cells synthesize plasminogen
- plasminogen is converted to plasmin, which breaks down fibrin |
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what is the major reason that injured or denuded vascular endothelium is prothrombotic?
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it exposes the collagen on the basement membrane
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how do platelets bind to collagen?
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by the secretion of von Willebrand's factor by injured vascular endothelium, which links the platelets to collagen
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what prothrombotic properties of injured vascular endothelium promote clotting?
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- tissue factor is secreted when induced by IL-1 or TNF from bacterial LPS. This activates the extrinsic clotting pathway
- endothelium has binding sites for clotting factors that stimulate coagulation |
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what two types of granules are in platelets and what do the chemicals inside those granules do?
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1. alpha granules: chemicals to initiate clotting
2. electron dense granules: inflammatory mediators and platelet aggregating factors |
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what three basic responses do platelets have when they contact ECM components?
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1. adhesion and change in shape
2. secretion of mediators 3. aggregation at site of injury |
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how does the morphology change in platelets and how do they adhere to the ECM of damaged vascular endothelium?
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- platelets form long pseudopods and spread out
- The ECM has proteins called von Willebrand's factor, to which the platelets have receptors and adhere. |
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When platelets encounter ECM from damaged endothelium, what is the end-product of the pathway that is initiated?
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thrombin
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What are the three most important chemical stimuli that promote platelet aggregation?
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1. ADP (inside platelet electron dense granules)
2. thromboxane A2 3. thrombin |
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what protein serves to link platelets together via a cross-linking reaction of their receptor sites?
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fibrinogen
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what the two major chemicals serve to inhibit/mediate platelet aggregation?
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1. prostacyclin (prostaglandin-I2)
2. nitric oxide |
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what is the biochemical surface on which coagulation reactions begin and what mineral is responsible for the surface binding?
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coagulation occurs on the phospholipid surface and is held together by Ca2+ ion
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what are the two pathways of the coagulation system and what activates one or the other?
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1. intrinsic pathway - surface contact with collagen, platelets, activates kinin components --> Hageman factor (XII)
2. extrinsic pathway - activated by Tissue Factor, a cellular lipoprotein released from damaged monocytes/endothelial cells --> Factor VII |
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what are the three types of anticoagulants and basically how do they work?
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1. antithrombins: inhibit the action of thrombin and other molecules by binding to heparin-like receptors on endothelium
2. proteins C and S: vitamin K dependent proteins that inactivate some clotting factors 3. plasminogen-plasmin: breaks down fibrin |
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what is a plasminogen activation inhibitor?
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Substances that are secreted by endothelial cells to inhibit the action of plasmin. Thus it is an anti-anti-coagulant.
Take-home message: there is fine control and redundancy in the coagulation/anticoagulation system |
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the formation of a clotted mass of blood within the uninterrupted circulatory system
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thrombosis
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what are the three major influences that contribute to thrombosis?
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1. injury to endothelium
2. alterations in normal blood flow 3. alterations in blood (hypercoagulability) |
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why do alteration in blood flow and stasis initiate thrombosis?
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- a change from laminar flow to turbulent flow will cause platelets to collide with the vessel wall, initiating a clot
- stasis prevents dilution by fresh blood and hepatic clearance of clotting factors. So, clots will spontaneously form. |
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what is a jet lesion?
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Damage to the vascular endothelium of the aorta caused by an aortic valve stenosis. The resulting turbulent jet of blood persisting against the aortic wall initiates formation of a thrombus.
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what are six common causes of vascular turbulence and stasis?
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1. indwelling catheters
2. positional stasis (like Turnpike Thrombosis) 3. stasis due to poor circulation and varicosities 4. heart valve stenoses 5. aneurysms 6. atherosclerotic plaques (not prevalant in vet med) |
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alteration in blood coagulation mechanism which predisposes to thrombosis
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hypercoagulability
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what are the two forms of hypercoagulability associated with thrombosis?
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1. primary (genetic) - defect in coagulation proteins
2. secondary - associated with various diseases such as renal failure and cancer |
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what are mural thrombi?
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thrombi attached to the wall of the heart and aorta
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proliferative inflammatiory alteration of the heart valve structure or pulmonary endothelium that can look like cauliflower
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vegetative endocarditis
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what are the four major "fates" of a thrombus?
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1. propagation - hit/obstruct a critical vessel
2. embolize - dislodge and flow downstream and lodge in a distant vessel 3. dissolve - fibrinolysis 4. organize/recanalize - become infiltrated with fibroblasts and form new channels with endothelial lining |
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what are six types of embolism
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1. pulmonary embolism
2. systemic embolism 3. cardiac embolism 4. septic embolism 5. air embolism 6. fat embolism |
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***what are the six major factors that determine the consequences of an infarction?
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1. size of compromized area
2. tissue and metabolite dependency 3. importance of physioligic role (e.g. brain, heart, muscle) 4. collateral circulation (tissue with redundant vascular supply) 5. tissue redundancy 6. rate of onset |
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what is a saddle thrombembolus?
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a thromembolism of both sides of an artery where there is a Y-junction, as in the iliac arteries.
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hypoperfusion of tissues due to reduction in blood volume, decreased cardiac output, or redistribution
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shock
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what is cardiogenic shock and some causes?
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shock caused by heart failure:
- myocardial infarction - arrhythmia - extrinsic pressure - outflow obstruction (e.g. pulmonary embolism) |
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what is hypovolemic shock and some causes?
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shock due to reduced blood volume to critical tissues
- hemorrhage - burns - trauma |
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what is septic shock?
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G+ or G- (most common due to LPS) septicemia
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what two ways does LPS cause damage, as in septic shock?
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1. direct injury to cells
2. initiation of synthesis, release, and secretion of mediators |
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what are five major steps in pathogenesis caused by mediators released during septic shock?
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1. myocardial dysfunction
2. vasodilation/hypotension 3. endothelial injury of microcirculation and lekuocyte aggregation 4. activation of the clotting system 5. lung, liver, kidney, and CNS failure |
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what is the major event in which LPS (endotoxin) activates septic shock?
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mononucleocytes/macrophages are activated and they release IL-1 and TNF-alpha
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basically, during LPS (endotoxin) induced septic shock, how do IL-1 and TNF-alpha lead to tissue damage?
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severe inflammation promotes intravascular coagulation and capillary thrombosis. This effect is a positive-feedback mechanism.
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***What are the three stages of septic shock?
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1. nonprogressive phase (compensatory - core perfusion)
2. progressive phase (increasing hypoperfusion) 3. irreversible phase (irreversible cell injury) |
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what is the basic reason that an animal may die from septic shock?
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rapid formation of microthrombi in capillaries leads to systemic coagulation and loss of perfusion
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an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change
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neoplasm
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a swelling that may or may not be neoplastic
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tumor
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what are the two basic components of all neoplasms?
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1. parenchyma - the population of neoplastic cells
2. supportive stroma - BVs and CT |
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benign tumor of a gland
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adenoma
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neoplasm derived from mesenchymal (connective tissue) elements
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sarcoma
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a malignant neoplasm of fibrous connective tissue
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fibrosarcoma
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malignant neoplasm of bone
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osteosarcoma
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malignant neoplasms of epithelial stem cell origin
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carcinoma
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carcinoma with a glandular morphological pattern
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adenocarcinoma
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a tumor derived from pluripotent stem cells
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mixed tumor
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a tumor consisting of all three embryonic germ cell layers
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teratoma
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malignant neoplasm of lymphoid tissue
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lymphoma
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carcinoma of seminiferous epithelium
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seminoma
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what are the five characteristics in evaluating benign and malignant neoplasms?
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1. degree of differentiation
2. degree of anaplasia 3. rate of growth 4. local invasiveness 5. presence or absence of metastases |
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the extent to which neoplastic cells resemble the normal population of cells they were derived from
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differentiation
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type of neoplasm that is poorly differentiated and more closely resembles the primitive stem cells from which it was derived
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anaplastic
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what are five histologic characteristics of cells used to determine the degree of differentiation?
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- cellular pleomorphism (cells have many different forms)
- staining characteristics - nuclear/cytoplasmic ratio - number of nucleoli and mitotic figures - cellular orientation |
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disorderly, but non-neoplastic growth of cells
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dysplasia
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what is functional differentiation?
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the degree that a neoplastic cell acts like a normal cell of derivation
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how does functional differentiation generally differ between benign and malignant neoplasms?
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in general, benign neoplasms are more likely to function like their normal, non-neoplastic counterparts than malignant cells
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how does growth rate generally differ between benign and malignant neoplasms?
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benign tumors tend to grow more slowly than malignant ones. Malignant tumors may grow erratically.
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in general, how does growth correlate with degree of differentiation?
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less differentiated cells tend to grow faster
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how would the growth rate of a tumor be calculated?
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the number of cells produced and living minus the number of cells dying
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how does local invasiveness generally differ between benign and malignant neoplasms?
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benign neoplasms tend to divide within themselves and can form a capsule whereas malignant neoplasms grow by invading and destroying surrounding tissue
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what is an "in situ carcinoma?"
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a carcinoma that has not invaded past the local basement membrane
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what is the surgical margin of a malignancy?
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the perimeter of encompassing the entirety of malignant cells that must be removed to prevent recurrence of that malignancy
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the spread of neoplastic cells from the primary (originating) lesion to distant sites
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metastasis
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what are the three major ways by which a neoplasm can metastatize?
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- blood stream
- lymphatic channels and nodes - direct implantation by contact |
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what are the four major factors that influence the ability of a neoplasm to metastatize?
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1. patterns of circulation
2. host immune defenses 3. favorable nutrient environment 4. presence of tissue receptors for tumor cells (such as chemokines) |
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what are the three important principles that explain the molecular basis of all neoplasms?
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1. they arise as a result of nonlethal genetic damage
2. regulatory genes are the target of damage 3. carcinogenesis is a multi-step process |
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what are the four major genetic apparatuses that when damaged, can cause cancer?
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1. growth-promoting genes
2. growth-inhibiting genes 3. apotosis controlling genes 4. genes controlling DNA repair |
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a normal gene which regulates cell growth and division
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protooncogene
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what are the seven major things that protooncogenes (may) code for?
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1. growth factors
2. competence factors (get cells in G0 and G1 for DNA synthesis) 3. progression factors (stimulate DNA synthesis in competent cells) 4. signal transduction proteins 5. second messenger/intracellular signalling proteins 6. transcription factors 7. cell cyclins (take home message: these genes control cell growth and division) |
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what are the two major cellular sites of (proto)oncoprotein activity?
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1. nucleus (gene regulation)
2. cell membrane (signal transduction) |
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a protooncogene that has been transformed into an uncontrolled gene
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oncogene
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what are the two major classes of oncogenes?
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1. v-onc: viral oncogenes (viral transduction)
2. c-onc: cellular oncogenes (intrinsic from mutations) |
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what is the fundamental difference between an oncoprotein and a protooncogene protein?
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oncoproteins are produced and behave independently of regulatory stimuli
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what are the five major steps in normal cell proliferation?
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1. GF binds to a specific receptor on the cell membrane
2. signal transduction is activated 3. second messengers affect induction/activation of transcription 4. DNA synthesis machinery is activated 5. cell division |
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how does mutation of GF protooncogenes into GF oncogenes affect cell division?
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- overexpression of GF causes an autocrine growth stimulation
- the mutated genes are not turned off so overproduction of GF and uncontrolled cell division occur |
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how does mutation of signal transduction pathways affect neoplasia?
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mutated signal transduction pathways result in persistent intracellular signalling and can lead to uncontrolled cell proliferation.
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what is the ras/c-ras (proto)ongogene?
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- ras is a normal protooncogene that regulates kinases that regulate GF production and DNA synthesis
- c-ras, the mutated form of ras, lacks a critical GTPase activity, and thus continually signals DNA synthesis and GF release |
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how can mutated nuclear regulatory factors influence neoplasia?
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- oncogenes such as c-myc continually stimulate cell division
- oncogenes such as c-rel and c-erbA inhibit cell differentiation and maturation |
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what important protooncogene is located on the mitochondria? What is the function of this gene? How can this gene lead to neoplasia?
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- bcl-2
- controls apoptosis - overexpression as an oncogene may extend survival - prolonged lifespan may allow other mutations in the cell |
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how do the upregulation and downregulation of bcl-2 affect a cell?
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(mitochondrial protooncogene)
- upregulation prevents apoptosis - downregulation allows apoptosis to occur |
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what are the two primary types of oncogene activation?
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1. changes in gene structure --> altered proteins
2. changes in gene regulation --> inappropriate gene expression |
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what are three important types of genetic mutations in oncogene activation?
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1. point mutations (e.g. in the ras gene)
2. chromosomal translocations (e.g. gene is moved away from its control segment, allowing unregulated expression; c-myc) 3. gene amplification - (e.g. c-myc and c-erb) are copied many times on a single segment of DNA |
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the ras gene expresses a protein that is involved in what type of cellular process?
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signal transduction
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in signal transduction oncoproteins such as c-src, c-abl, and c-raf, what is a common biochemical reaction that leads to neoplasia?
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unregulated kinase activity - the signal transduction is always "on", even without a stimulus.
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when the ras gene is activated, what is its function?
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ras activates cytoplasmic kinases, which in turn turn on DNA synthesis and release of growth factors.
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how does c-ras cause neoplasia?
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since the gene involves synthesis and release of growth factors, the unregulated oncogene/oncoprotein can have an autocrine function, which causes uncontrolled growth.
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what is specific about the mutation in ras to c-ras that causes it to become unregulated?
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ras protein has an intrinsic GTPase activity that when it cleaves GTP to GDP, inactiates the ras machinery. c-ras lacks this GTPase and thus never turns off.
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what is the basic function of the myc, myb, jun, and fos protooncogenes?
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they regulate DNA transcription/cycling in the cell nucleus
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how do c-rel and c-erbA gene lead to neoplasia?
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they inhibit cell differentiation and maturation
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in what two ways can chromosomal translocations lead to oncogene activation?
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- the gene can be moved away from a control segment
- the gene can be moved near a promoter segment |
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what is Burkitt's lymphoma?
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translocation of the c-myc gene to a place where Ig heavy chain expression is controlled. This results in uncontrolled transcription of growth factor genes.
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how does gene amplification, such as in c-myc, cause neoplasia?
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Multiple duplications of the myc gene occur on the chromosome. This will lead to many more sites of expression of growth factor genes.
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what is the main function of the myc gene?
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to control the expression of growth factor genes.
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what is the basic function of suppressor genes?
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control cell growth ("the brakes")
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what is a retinoblastoma, what is a common gene mutation that causes this tumor, and why does this mutation cause neoplasia?
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- a neoplasm arising from the retina
- the Rb gene is mutated - this gene is a supporessor gene, so mutation will stop the regulation of cell growth. ("the brakes" on the cell cycle fail) |
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why is retinoblastoma more prevalent for those that are heterozygous for the mutated gene versus those that are homozygous for the non-mutated gene, even though the non-mutated gene is autosomal dominant?
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retinoblastoma requires both Rb genes to be mutated. In heterozygotes, only one Rb gene must be damaged to activate the oncogene, whereas in homozygotes with the non-mutated gene would require two mutations. The latter has a much lower probablility
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what is a recessive cancer gene?
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an oncogene that is required to be homozygous to cause neoplasia.
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how do cell surface molecules produced by suppressor genes such as DCC regulate cell growth? How would mutation of DCC lead to neoplasia?
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they foster contact inhibition. For example, if cells are touching, they are signaled to stop growing. A mutation would lead to loss of contact inhibition, so the presence of neighboring cells would not stop tumor growth.
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how does the lifespan of a cell relate to neoplasia?
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If a cell is able to divide, the longer a cell is alive, the higher chance it will develop a mutation that will cause neoplasia and uncontrolled division.
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true or false: a single mutation can create an oncogene capable of causing carcinogenesis?
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False. Whereas a single mutation can create an oncogene, cancer is a multi-step process that requires several cooperating oncogenes.
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an agent that is able to damage the genetic machinery, resulting in heritable, nonlethal mutation that gives rise to tumors
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carcinogen
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what are the three primary types of carcinogens?
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1. chemicals
2. radiation 3. transforming viruses |
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what are the two primary modes of action of chemical carcinogens and what is the difference?
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1. direct acting - does not require metabolism to cause mutation
2. indirect acting - the metabolite of the carcinogen causes mutation |
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what is the primary site of indirect activation of chemical carcinogens?
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liver
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for a typical chemical carcinogen, what are the two basic steps that lead to carcinogenesis? What do these steps do?
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1. initiation - formation of a stable, NONLETHAL mutation in a protooncogene or a suppressor gene
2. promotion - steps/factors which foster the expression of carcinogenesis |
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what is a promoter with respect to chemical carcinogenesis?
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chemicals that are not carcinogens themselves but foster mutation or the expression of mutation.
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how does the order of exposure and timing of initiators and promotors affect tumor formation?
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- the initiator must precede the promoter
- exposure to both the promoter and inititiator are required to form a tumor - exposure to promoter does not necessarily have to immediately occur after exposure to initiator; the initiator can "wait" for the promoter - exposure to the promoter in sufficiently high levels and/or frequency is required for tumor formation |
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why can high levels of toxic agents that cause mutation not lead to neoplasia?
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because severely damaged DNA cannot replicate. The mutation must be "fixed" by DNA repair mechanisms for the DNA to be replicable.
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What are the three major effects of promoters in chemical carcinogenesis?
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1. induce proliferation of cells that have reduced requirements for growth factors
2. induce proliferation of cells which have lost the ability to respond to growth inhibitory signals 3. may facilitate development of additional mutations |
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why does pulmonary asbestosis lead to neoplasia and how do irritants such as tobacco smoke make this worse?
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deposition of asbestos fibers lead to chronic inflammation and secretion of excessive growth factors like EGF. Tobacco smoke is an additional irritant and may act as an initiator, with the asbestos as the promoter.
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what are six diseases associated with asbestos expsoure?
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1. chronic fibrosis
2. chronic inflammation 3. mesothelioma 4. immunosuppression 5. gastric carcinoma 6. colonic carcinoma |
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in what six ways can UV irradiation have carcinogenic effects?
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1. inactivate intracellular enzymes
2. inhibit cell growth 3. induce mutations 4. kill cells directly 5. inhibit immune response 6. have a promoter action |
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by what three major ways can the body prevent damage caused by UV irradiation?
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1. cutaneous pigments
2. aromatic portions of amino and nucleic acids absorb irradiation 3. free radical scavengers |
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***what types of radiation cause damage in cells?
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ionizing radiation: alpha, beta, gamma, x-ray
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what are the five critical phases in the genesis and proliferation of a neoplasm?
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1. transformation to a neoplastic cell via mutation
2. growth from one neoplastic cell to many 3. local invasion by neoplastic cells 4. +/- distant metastasis 5. death of tumor cells |
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true or false: most tumor cells have a shortened doubling time with respect to their normal counterparts?
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false. Most have equal or longer doubling times.
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what is the growth fraction of a neoplasm?
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the proportion of cells in the proliferative pool (G1 cells)
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what four pathways can dividing neoplastic cells take that will affect the growth rate of a tumor?
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1. divide - in the proliferative pool
2. die - nonproliferative pool 3. differentiate - nonproliferative pool 4. do dormant (G0) - nonproliferative pool |
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period of time from occurrence of first tumor cell to clinically detectable tumor
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tumor latency
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the evolution, over time, of a phenotypically diverse population of neoplastic cells
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progression
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by what process does progression of a tumor work and what are its effects?
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Progresses by a Darwinian "survival of the fittest"
tumor will become more malignant over time |
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what are the three major factors in successful tumor progression?
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1. clonal selection of successful clones
2. rate of subclone generation 3. continued mutation of unstable genome |
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how large can a tumor become before it needs a blood supply?
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1-2 mm
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what triggers angiogenesis in tumors?
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- tumors secrete angiogenic factors
- local inflammation promotes angiogenesis |
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what are the two main phases of invasion by tumors?
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1. invasion of ECM
2. vascular dissemination and homing |
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what are the four stages of tumor invasion of ECM?
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1. detachment from main tumor mass
2. attachment to ECM (to laminin and fibronectin) 3. degradation of ECM 4. migration |
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why can tumor cells so readily detach from the main tumor mass?
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there is no contact inhibition stopping tumor growth.
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in what two ways does a tumor cell degrade the ECM
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1. secretes proteases
2. indices host cells (fibroblasts, macrophages) to secrete proteases |
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how does a tumor cell migrate through a degraded ECM?
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secretes autocrine motility factors and moves in a pseudopod-like motion
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what are the five basic steps in tumor metastasis?
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1. clonal expansion and angiogenesis
2. intravasation 3. adhesion of a tumor cell embolus to the BV basement membrane 4. extravasation 5. repeat step 1 |
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what are the two basic types of antigens produced by tumors?
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1. tumor specific antigens (TSA) - only on tumor cells
2. tumor associated antigens (TAA) - found on normal and neoplastic cells |
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what is the difference between TSAs and TAAs in cancer immunity?
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TSA = tumor specific antigen: elicits an immune response
TAA = tumor associated antigen: recognized as 'self' and does not elicit an immune response |
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what is an oncofetal antigen?
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a gene normally expressed during embryogenesis that can be expressed by tumor cells (e.g. alpha-fetoprotein and carcinoembryonic antigen, CEA)
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what are the major five types of cells and proteins that kill tumor cells?
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cytotoxic T cells, NK cells, macrophages (TNF), antibodies, complement
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***what is the greatest risk factor for cancer and what are some causes of this risk factor?
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Immunocompromised individuals
- AIDS, FeLV - corticosteroids - degenerative diseases - age |
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what are six ways that tumors can overcome the immune system?
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1. growth of antigen-negative variants
2. reduced expression of MHC 3. shedding and modulation of antigens 4. natural and therapeutic immunosuppression 5. blocking antibodies 6. cloaking with cells/platelets Take home message: survival of the fittest |
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***progressive loss of body mass accompanied by weakness, anorexia, anemia
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cachexia
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what is paraneoplastic syndrome? What are some symptoms?
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symptoms of neoplasia that are not directly related to tumor growth.
- inappropriate hormone production - osseus metaplasia of soft tissue - neuromuscular failure - thrombosis and anemia - hypercalcemia (the #1 cause of hypercalcemia is the presence of a tumor) |
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what are the two basic characterizations of cancer (mostly used in human medicine)
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- grading - establish estimate of tumor aggressiveness based on cytology and # of mitoses
- staging - based on size of primary lesion, involvement of nodes, metastases |
