patho exam 4 Flashcards

Question

3. Membrane Damage

Answer 1

◼ Most forms of cell injury that end in cell death: characterized by increased membrane permeability → membrane damage ◼ Cell membranes may be damaged by: ROS, phospholipid biosynthesis, degradation, cytoskeletal abnormalities that disrupt the anchors for plasma membranes ◼ Most important sites of membrane damage: Mitochondrial membrane damage Plasma membrane damage Injury to lysosomal membranes

Answer 2

Importance of intracellular [Ca2+] ◼ Cellular messenger ◼ Stored in ER and mitochondria Normally, intracellular [Ca2+] low vs. extracellular levels ◼ Maintained by Ca2+/Mg2+-ATPase exchange system Toxins and ischemia can increase intracellular [Ca2+] ◼ Cell damage from activated enzymes: phospho- lipases, proteases, ATPases, endonucleases

Answer 3

Protein synthesis in ER: chaperones enhance proper folding of newly synthesized proteins ◼ Process is imperfect; some misfolded polypeptides made ◼ Targeted for proteolysis by ubiquitination Accumulated misfolded proteins in ER induce protective cellular (adaptive) response = unfolded protein response ◼ Activates signaling pathways that increase the production of chaperones and retard protein translation, reducing levels of misfolded proteins ◼ If quantity of misfolded protein exceeds capacity of adaptive response, additional signals activate proapoptotic sensors →apoptosis (intrinsic, more later)

Answer 4

DNA damage may result from: ◼ Exposure of cells to radiation or chemotherapeutic agents ◼ Intracellular generation of ROS ◼ Acquisition of mutations If severe damage: may trigger apoptotic death Damage to DNA sensed by intracellular sentinel proteins, which transmit signals that lead to the accumulation of p53 protein ◼ p53 first arrests the cell cycle (at the G1 phase) to allow the DNA to be repaired before it is replicated ◼ If the damage is too great to be repaired successfully, p53 triggers apoptosis, mainly by the mitochondrial pathway

Answer 5

Two patterns visible under microscope: ◼ Cellular swelling ◼ Impaired Na+/K+-ATPase pump, usually from hypoxia ◼ Fatty change: indicative of severe injury ◼ Many small vacuoles of fat in cytoplasm ◼ May be due to high fat load or reduced ability to metabolize fat ◼ Liver, heart, kidneys particularly susceptible

Answer 6

Balance exists between death and proliferation Cell death in two ways: ◼ Apoptosis: controlled cell destruction (“cell suicide”) ◼ Removes cells that are being replaced or have “worn out” ◼ Removes unwanted tissue ◼ Normal process in the body ◼ Necrosis: Unregulated death caused by injuries to cells; death of organ or tissue that is part of a living person ◼ Cells swell and rupture ◼ Inflammation results

Answer 7

cell size - enlarged (swelling) nucleus - pyknosis to karyorrhexis to karyolysis plasma membrane - disrupted cellular contents - enzymatic digestion; may leak out of the cell adjacent inflammation - frequent physiologic or pathologic role - invariably pathologic (culmination of irreversible cell injury)

Answer 8

cell size - reduced (shrinkage) nucleus - fragmentation into nucleosome-sized fragments plasma membrane - intact; altered structure, esp. orientation of lipids cellular contents - intact; maybe released in apoptotic bodies adjacent inflammation - no physiologic or pathologic role - often physiological means of eliminating unwanted cells; may be pathologic after some forms of cell injury, esp. DNA & protein damage

Answer 9

◼ Programmed cell death via controlled cell destruction ◼ Physiologic: ◼ Development, maturation, repair ◼ Pathophysiologic: ◼ Lack of apoptosis in proliferation of CA cells ◼ Hepatocyte death in hepatitis B and C ◼ Control Mechanism: unclear

Answer 10

◼ Controlled autodigestion via endogenous enzymes ◼ Cell shrinkage: ◼ Disruption of cytoskeleton ◼ Condensation of cytoplasmic organelles ◼ Disruption and clumping of nuclear DNA ◼ Eventually nucleus breaks into spheres ◼ Wrinkling of cell membrane ◼ Finally: division of cell into membrane-covered fragment

Answer 11

Necrosis: death of organ or tissue that is part of a living person Unregulated: ◼ Enzymatic digestion of cell components ◼ Loss of membrane integrity ◼ Uncontrolled release of products into intracellular space ◼ Initiation of inflammatory response

Answer 12

Liquefaction/liquefactive necrosis: e.g., center of abscess ◼ Characterized by tissue softening ◼ Death of some cells but their catalytic enzymes still functional Coagulation necrosis: e.g., hypoxic injury/infarct ◼ Transformation into gray, firm mass ◼ Acidosis, with resultant denaturation of proteins Caseous necrosis: e.g., Tb granulomas ◼ Persistence of dead cells as soft, cheeselike debris

Answer 13

Fat necrosis: Focal areas of fat destruction (due to abdominal trauma or acute pancreatitis) ◼ Enzymes leak out of damaged pancreas, digest peritoneal fat cells and their contents (e.g., stored triglycerides) ◼ Released fatty acids combine w/ Ca2+: produce grossly identifiable chalky white lesions Fibrinoid necrosis: Special form of necrosis, visible by light microscopy ◼ Seen in immune reactions, in which Ag/Ab deposited bv walls, and in severe hypertension

Answer 14

Describes large area of necrotic tissue 2 classifications: ◼ Dry gangrene: lack of arterial blood supply but venous flow can carry fluid out of tissue ◼ Tissue tends to coagulate ◼ Moist (wet) gangrene: lack of venous flow lets fluid accumulate in tissue ◼ Tissue tends to liquefy; infection likely ◼ Special type: ◼ Gas gangrene: Clostridium infection produces toxins and H2S bubbles

Answer 15

Autophagy (“self-eating”): lysosomal digestion of the cell’s own components ◼ Survival mechanism during nutrient deprivation ◼ Enables starved cell to live by eating its own contents and recycling these contents to provide nutrients and E Intracellular organelles and cytosol sequestered within an ER-derived double membrane (phagophore); matures into autophagic vacuole ◼ Fuses w/ lysosomes: forms autophagolysosome ◼ Digests cellular components w/in

Answer 16

Is it programmed into cells? ◼ Telomeres become too short; cell can no longer divide Is it the result of accumulated damage? ◼ Older cells have more DNA damage ◼ Older cells have more free radicals ◼ Cells lose the ability to repair their telomeres

Answer 17

Results from combination of multiple and progressive cellular alterations ◼ Accumulation of DNA damage and mutations ◼ Replicative senescence: reduced capacity of cells to divide secondary to progressive shortening of chromosomal ends (telomeres) ◼ Defective protein homeostasis: loss of normal proteins and accumulation of misfolded proteins Exacerbated by chronic diseases, especially those associated with prolonged inflammation, and by stress; slowed down by calorie restriction and exercise

Answer 18

STRESSOR - Interferes with normal cell function CELL INJURY or ADAPTATION or COUNTERATTACK CELL INJURY - Decreases cell function ADAPTATION - Cell or system reacts to restore normal function COUNTERATTACK - Cells and systems react to reduce or remove the stressor cell injury to HEALING healing - Repairs injury CELL INJURY or ADAPTATION or COUNTERATTACK can all go to signs & symptoms SIGNS: Can be detected or measured SYMPTOMS: The patient can feel COMPLICATIONS: Occur when injury, adaptation, and counterattacks act as new stressors

Answer 19

◼ Reaction of vascularized tissue to local injury ◼ Reaction develops in steps: 1. recognition of the offending agent; 2. recruitment of blood cells and proteins to the site; 3. removal of the offending agent; 4. regulation of the reaction; 5. repair of injured tissue

Answer 20

Many and varied ◼ Response to infectious microorganisms ◼ Trauma ◼ Surgery ◼ Caustic chemicals ◼ Heat and cold extremes ◼ Ischemic damage to tissues ◼ Immune rxns (hypersensitivity, autoimmunity)

Answer 21

Difference dependent upon: ◼ Persistence of injury ◼ Clinical symptoms ◼ Nature of the inflammatory response Acute: ◼ Accumulation of fluid and plasma components in tissue ◼ Intravascular stimulation of platelets ◼ Presence of PMNs Chronic: ◼ Lymphocytes, plasma cells, macrophages

Answer 22

onset - fast: minutes to hours cellular infiltrate - mainly neutrophils (PMNs) tissue injury - usually mild and self-limited fibrosis - none local & systemic signs - prominent

Answer 23

onset - slow: days cellular infiltrate - monocytes/macrophages; lymphocytes tissue injury - may be significant fibrosis - maybe severe and progressive local & systemic signs - variable; usually modest

Answer 24

Short: minutes to days Hallmarks: ◼ Rubor (redness) ◼ Dolor (pain) ◼ Calor (heat) ◼ Tumor (swelling) ◼ Functio laesa (loss of function) Anything ending in –itis: describes an inflammatory state

Answer 25

Outcomes: ◼ Resolution ◼ Abscess ◼ Scar ◼ Persistent inflammation Stages: ◼ Vascular (hemodynamic) stage ◼ Cellular stage

Answer 26

Vascular stage: ◼ Transient vasoconstriction ◼ Rapid vasodilation of arterioles and venules supplying injured area ◼ Increased permeability of vessel endothelial cell barrier Cellular stage: ◼ PMNs initially ◼ Macrophages later

Answer 27

Chemotactic factors to Margination & adherence to Emigration to Chemotactic migration to Phagocytosis

Answer 28

Tissue injury *Trauma *Ischemia *Neoplasm *Infection *Particle (e.g., asbestos) Vasoactive mediators *Histamine *Serotonin *Bradykinin *Anaphylatoxins *Leukotrienes/prostaglandins *Platelet activating factor Chemotactic factors *C5a *Lipoxygenase products (e.g., LTB4) *Formylated products *Lymphokines *Monokines

Answer 29

◼ Histamine ◼ Serotonin ◼ Bradykinin ◼ Anaphylatoxins ◼ Leukotrienes/prostaglandins ◼ Platelet activating factor to Increased vascular permeability to edema

Answer 30

◼ Histamine ◼ Serotonin ◼ Bradykinin ◼ Anaphylatoxins ◼ Leukotrienes/prostaglandins ◼ Platelet-activating factor to Recruitment and stimulation of inflammatory cells can either go to acute inflammation or chronic inflammation Acute inflammation *PMNs *Macrophages Chronic inflammation *Macrophages *Lymphocytes *Plasma cells

Answer 31

plasma - Complement activation: Anaphylatoxins (C3a, C5a) ◼ Hageman factor activation: Bradykinin cell ◼ Mast cell/basophil degranulation: Histamine ◼ Platelets: Serotonin ◼ Inflammatory cells: Leukotrienes, prostaglandins, platelet-activating factor

Answer 32

plasma ◼ Complement activation: C5a, C3a cell ◼ Cell membrane phospholipids: Lipoxygenase products (e.g., LTB4) ◼ Inflammatory cells: Chemokines = Lymphokines, monokines ◼ Bacterial and mitochondrial: Formylated products

Answer 33

Arachidonic acid released from injured cell membranes to Cyclooxygenase/ Lipoxygenase pathways Prostaglandins/ leukotrienes to vasodilation and increased capillary permeability histamine released from injured cells can go to Vasodilation and increased capillary permeability Vasodilation and increased capillary permeability can go to calor (heat) or rubor (redness) Vasodilation and increased capillary permeability to exudate exudate to tumor or dolor (pain) exudate to toxin dilution exudate to Decreased blood flow out of injured area

Answer 34

Phagocytes enter injured area by: - margination - pavementing - emigration - chemotaxis chart (how do you study this ah....)

Answer 35

histamine - sources: mast cells, basophils, platelets - actions: vasodilation, increased vascular permeability, endothelial activation prostaglandins - sources: mast cells, leukocytes - actions: vasodilation, pain, fever leukotrienes - sources: mast cells, leukocytes - actions: increased vascular permeability, endothelial activation chemotaxis, leukocyte adhesion, and activation cytokines (ex: TNF, IL-1, IL-6) - sources: macrophages, endothelial cells, mast cells - actions: local: endothelial activation (expression of adhesion molecules); systemic: fever, metabolic abnormalities, hypotension (shock) chemokines - sources: leukocytes, activated macrophages - actions: chemotaxis, leukocyte activation platelet-activating factor - sources: leukocytes, mast cells - actions: vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst complement - sources: plasma (produced in the liver) - actions: leukocyte chemotaxis and activation, direct target killing (membrane attack complex), vasodilation (mast cell stimulation) kinins - sources: plasma (produced in the liver) - actions: increased vascular permeability, smooth muscle contraction, vasodilation, pain

Answer 36

vasodilation: - eicosanoids: prostaglandins PG12 (prostacyclin), PGE1, PGE2, PGD2 Vasoconstriction - eicosanoids: thromboxane A2, Leukotrienes C4, D4, E4 increased vascular permeability - eicosanoids: leukotrienes C4, D4, E4 Chemotaxis, leukocyte adhesion - eicosanoids: leukotriene B4

Answer 37

Acute inflammation - injury: tissue necrosis, bacterial infection, toxins, trauma - vascular changes: vasodilation, increased vascular permeability healing: resolution & scarring (fibrosis) resolution: clearance of harmful stimuli, clearance of mediators and acute inflammatory cells, replacement of injured cells, normal function scarring: loss of function, connective tissue, fibroblasts or from acute inflammation, the cell can go to chronic inflammation and then can go to scarring with chronic inflammation - chronic infectious - persistent injury - autoimmune and allergic disease

Answer 38

The inflammatory response ◼ Acute inflammation ◼ Chronic inflammation ◼ Manifestations of inflammation Tissue repair and wound healing ◼ Tissue repair ◼ Wound healing

Answer 39

Long and self-perpetuating: weeks to years ◼ Contains and removes pathologic agent/process Characteristic cells: ◼ Macrophages ◼ Lymphocytes ◼ Fibroblasts: increased risk of scarring and deformity than acute inflammation Typical causative agents: ◼ Recurrent or progressive acute inflammation ◼ Low-grade, persistent irritants, with the inability to penetrate deeply or spread rapidly

Answer 40

Two patterns: ◼ Nonspecific chronic inflammation ◼ Granulomatous inflammation

Answer 41

The inflammatory response ◼ Acute inflammation ◼ Chronic inflammation ◼ Manifestations of inflammation Tissue repair and wound healing ◼ Tissue repair ◼ Wound healing

Answer 42

Local ◼ Swelling ◼ Exudates: serous, hemorrhagic, fibrinous, membranous, purulent (suppurative) ◼ Abscess ◼ Ulceration Systemic ◼ Acute-phase response ◼ Alterations in WBC count ◼ Fever

Answer 43

Leukocytes release interleukins and tumor necrosis factor ◼ Affect thermoregulatory center → fever ◼ Affect central nervous system → lethargy ◼ Skeletal muscle breakdown Liver makes fibrinogen and C-reactive protein ◼ Facilitate clotting ◼ Bind to pathogens ◼ Moderate inflammatory responses

Answer 44

tissue regeneration: repair of injured tissue with cells of same parenchymal type ◼ Parenchymal tissue ◼ Stromal tissue ◼ Labile cells ◼ Stable cells ◼ Permanent (fixed) cells Connective tissue repair: scar tissue substituted for parenchymal cells of injured tissue

Answer 45

Healing depends upon extent of tissue loss and occurs via: ◼ Primary intention ◼ Secondary intention Phases of healing: ◼ Inflammatory phase: just seen ◼ Proliferation phase: Angiogenesis and growth of granulation tissue; emigration of fibroblasts and deposition of extracellular matrix ◼ Remodeling phase: Maturation and reorganization of the fibrous tissue

Answer 46

◼ Malnutrition ◼ Blood flow and O2 delivery ◼ Impaired inflammation and immune responses ◼ Infection, wound separation, foreign bodies ◼ Age

Answer 47

Cell cycle ◼ G1: RNA and protein synthesis and cell growth; variable time* ◼ S: DNA synthesis w/ 2 sets of chromosomes; 10 – 20 hours ◼ G2: premitotic; 2 – 10 hours ◼ M: mitosis; 0.5 – 1 hour ◼ G0: resting phase; variable time* * Duration is dependent upon tissue type

Answer 48

Labile cells: cells that continuously multiply and divide throughout life. Labile cells replace the cells that are lost from the body. Cyclins - ensure the cell has made proteins needed for chromo-some separation - check for correct DNA duplication - measure whether the cell is large enough to divide

Answer 49

Role in regu- lating G1–S check- point of cell cycle

Answer 50

Cell proliferation: process by which cells divide and reproduce 3 general types of cells with regard to differentiation ◼ Highly differentiated ◼ Progenitor cells ◼ Stem cells

Answer 51

Cell differentiation: Orderly, stepwise process Progenitor cells: partially differentiated, replace mature cells of same cell lineage Stem cells: ◼ Unipotent - red blood cell ◼ Oligopotent - myeloid cell ◼ Pluripotent - stem cell, can becom anything

Answer 52

Tumor: any condition leading to swelling but often used to mean neoplasm Neoplasm: abnormal mass of tissue in which growth exceeds, and is uncoordinated with, that of normal tissues ◼ Benign: well-differentiated cells, clustered together in a single mass; usually do not cause death ◼ Malignant: less well differentiated, can break loose (metastasize); death if untreated or uncontrolled ◼ -oma: suffix added to parenchymal tissue type to denote tumor name

Answer 53

Benign - Cell characteristics: Well- differentiated; resemble cells in tissue of origin - Rate of growth: Progressive and slow; may stop or regress - Mode of growth: Expansion w/o invasion; usually encapsulated - Metastasis: No Malignant - Cell characteristics: undifferentiated; Undifferentiated, w/ anaplasia and atypical structure; little or no resemblance to tissue of origin - Rate of growth: Variable, depends on the level of differentiation - Mode of growth: invasive; sends out processes to infiltrate surrounding tissues - Metastasis: yes

Answer 54

◼ When differentiated, “working” cells mutate, they form differentiated “working” tumors— benign tumors ◼ When undifferentiated, rapidly dividing cells mutate, they form rapidly dividing tumors—malignant tumors

Answer 55

Fail to undergo normal cell proliferation and differentiation ◼ Believed that cancer cells develop from mutations occurring during differentiation ◼ Mutations early in process: tumor poorly differentiated and highly malignant ◼ Mutations later in process: tumor more fully differentiated and less malignant ◼ Grading of tumor based upon degree of differentiation and number of proliferating cells

Answer 56

look at histology to see what they look like anxd to seeif they look like normal cells ◼ Loss of contact inhibition ◼ Loss of cohesiveness and adhesion ◼ Impaired cell-cell communication ◼ Expression of altered tissue antigens ◼ Production of degradative enzymes - Allowing invasion and metastasis

Answer 57

deregulatinng cellular energetics sustaining proliferative signaling inducing angiogenesis resisting cell death genomic instability (mutator phenotype) activing invasion and metastaus tumro promoting inflammation enabling immortality evading growth suppressors avdoing immune destruction

Answer 58

Seeding ◼ Entering body cavity Metastasis ◼ Leave 1o tumor ◼ Invade ECM ◼ Enter blood/lymph ◼ Survive blood/lymph ◼ Location for growth ◼ Invade tissue & grow

Answer 59

Depends upon: ◼ Number of cells dividing ◼ Duration of cell cycle ◼ Number of cells being lost compared to number being produced Tumor growth due to increased number of dividing cells ◼ Cells don’t die on schedule ◼ Lack growth factors for entering Go phase Growth limited by blood supply and nutrients

Answer 60

genetic mxm whereby normal cells are transformed into cancer cells Proto-oncogenes ◼ Growth stimulating regulatory genes ◼ Usually encode growth factors or second messengers that stimulate growth Tumor suppressor genes (anti-oncogenes) ◼ Growth inhibiting regulatory genes Genes controlling apoptosis DNA repair genes

Answer 61

◼ Multi-step process whereby normal cells become cancer cells ◼ Initiation ◼ Promotion ◼ Progression

Answer 62

◼ Interactions among multiple risk factors or repeated exposure to carcinogens necessary for cancer to develop ◼ Hereditary ◼ Hormones ◼ Obesity ◼ Chemical carcinogens ◼ Radiation ◼ Viruses ◼ Immune dysfunction

Answer 63

◼ Changes in organ function (e.g., organ damage, inflammation, and failure) ◼ Local effects of tumors (e.g., compression of nerves or veins, gastrointestinal obstruction) ◼ Tissue integrity: nonspecific signs of tissue breakdown (e.g., protein wasting, bone breakdown) ◼ Paraneoplastic syndromes: Ectopic hormones secreted by tumor cells

Answer 64

Cancer cachexia ◼ Weight loss ◼ Muscle wasting ◼ Weakness ◼ Anorexia ◼ Anemia

Answer 65

◼ Surgery ◼ Radiation ◼ Chemotherapy ◼ Hormonal ◼ Biotherapy (immunotherapy, biologic response modifiers) ◼ Targeted ◼ Transplantation ◼ Hyperthermia ◼ Photodynamic