Pathology Lecture 1 And 2: Cell Injury, Adaptation, And Death

Front 1

What are the 4 classifications of disease?

Back 1

1. Developmental
2. Inflammatory
3. Neoplasmic
4. Degenerative

Front 2

Pathognomonic

Back 2

a sign or symptom that is unique for a particular disease

Front 3

Syndrome

Back 3

a group of signs and symptoms that characterize a particular disease or disorder

Front 4

Prevalence

Back 4

number of individuals in a specific location currently having a particular disease

Front 5

Incidence

Back 5

Number of new cases of a disease (usually on an annual basis) in a given population

Front 6

stagnant hypoxia

Back 6

reduced venous drainage interfering with oxygenation

Front 7

histotoxic hypoxia

Back 7

failure of the ETC system (cyanide poisoning)

Front 8

How do cells differ in their response to anoxia?

Back 8

1. neurons die after 3-5 minutes
2. Myocardial cells may survive 30-60 mins under ideal conditions
3. Hepatic and renal tubular cells 1-2 hrs
4. a leg may last for many hours

Front 9

What are the 2 classes of toxic substances/chemical agents?

Back 9

1. Those that directly interact w/ cells w/out requiring metabolic activation

2. those that are not toxic themselves, but are metabolized to yield a toxin

Front 10

Examples of Toxic substances that directly interact w/ cells w/out requiring metabolic activation

Back 10

1. Heavy metals and cyanide--> mito

2. Phalloidin and taxol --> cytoskeleton

3. Chemo alkylating agents --> DNA

Front 11

Carbon tetrachloride

Back 11

-metabolized in the liver--> chloride ion and a highly toxic free radical (trichloromethyl) which damages hepatocytes

Front 12

Acetaminophen

Back 12

-an important constituent of many analgesics, detoxified in the liver

-however, large doses can overwhelm the detox mechanism and toxic products of the process accumulate--> destroy hepatocytes

Front 13

Examples of Secondary nutritional deficiencies:

Back 13

1. Increased requirement
2. Defective absorption
3. Defective utilization (liver disease)

Front 14

epigenetics

Back 14

-genetic function is changed w/out changing the genes themselves

-ex DNA methylation

Front 15

Mitochondrial permeability transition: MPT

Back 15

-a nonselective inner membrane channel that disrupts the proton gradient required for oxidative phosphorylation, allows Ca and other substances to leak into the cytosol

Front 16

Summary of damage to Mitochondrias

Back 16

-can result in cell damage and death (cytochrome c --> apoptosis) by compromising ATP production, disrupting Ca homeostasis, increasing oxidative stress and activating apoptotic pathways

Front 17

4 important O2 derived free radicals

Back 17

1. hydroxyl radical
2. superoxide anion
3. hydrogen peroxide
4. hypoclorite ion

Front 18

What are 4 sources of free radicals?

Back 18

1. Oxidation-reduction rxns
2. Nitric oxide
3. Radiation
4. metabolism of exogenous chemicals (carbon tetrachloride)

Front 19

Lipid peroxidation of membranes

Back 19

-oxidative degradation of lipids, free radicals react w/ lipids in cell membranes--> cell damage
-most often affects polyunsat FA b/c they have multiple double bonds

Front 20

What is a common 1st rxn of lipid peroxidation?

Back 20

hydroxyl ion abstracts a hydrogen to make water and FA radical

-this leads to chain rxn--> increased # of FA radicals formed--> cell memb destruction

Front 21

Oxidative modification of proteins

Back 21

free radicals promote:
1. oxidation of AA side chains of prots
2. formation of prot-prot cross linking
3. oxidation of the protein backbone--> fragmentation
-distrupt enz activity and structural architecture of the cell

Front 22

Superoxide dismutases

Back 22

enzymes found in the cytosol and mito that catalyzes the conversion of superoxide to hydrogen peroxide and O2

Front 23

Catalase

Back 23

present in peroxisomes, catalzyes the breakdown of H2O2 to water and O2

Front 24

Glutathione peroxidase

Back 24

catalyzes the conversion of the hydroxyl radical to water and the glutathione homodimer (GSSG)

Front 25

Antioxidants

Back 25

vitamins A, E, C and B-carotene may block the formation of free rads or scavenge them once formed

Front 26

Primary lysosomes

Back 26

IC organelles containing catabolic enzymes, fuse w/ vacuoles containing material to be digested

Front 27

Phagolysosome (secondary lysosome)

Back 27

here digestion and the killing of microorganisms takes place

Front 28

Lysosomal storage diseases

Back 28

inherited lack of certain catabolic lysosomal enzymes result in the abnormal accumulation of the substrates of those enzymes

Front 29

Xanthomas

Back 29

accumulations of foam cells that form masses beneath the skin, happens in diseases involving high levels of serum choleterol

-foam cells may contain debris such as triglycerides, cholesterol and cholesterol esters

Front 30

Russell Bodies

Back 30

accumulation of immunoglobulins in plasma cells result in rounded eosinophilic structures

Front 31

Mallory bodies

Back 31

accumulation of proteins in liver cells as a result of alcoholism form characteristic eosinophilic deposits

Front 32

Hemosiderin

Back 32

golden yellow to brown deposits derived from breakdwon of hemoglobin in cells and tissues when there is a local or systemic excess of iron

Front 33

Hemosiderosis

Back 33

a condition in which hemosiderin is confined mainly to macrophages and is not associated w/ tissue or organ damage

Front 34

Hemochromatosis

Back 34

an extensive accumulation of hemosiderin often involving parenchymal cells and tissue damage

Front 35

Dystrophic calcification

Back 35

deposition of Ca phosphate in necrotic tissues

-serum levels of Ca and P can be normal

Front 36

Metastic calcification

Back 36

deposition of Ca-Phosphate in normal tissues when Ca and/or phosphate serum levels are high

Front 37

Major causes of hypercalcemia

Back 37

1. Primary hyperparathyroidism
2. Increased destruction of bone
3. Vit D toxicity
4. Renal failure -secondary hyperparathyroidism

Front 38

Major causes of hyperphospatemia

Back 38

1. Primary hypoparathyroidism

2. Renal insufficiency

Front 39

What are the 5 basic types of cellular adaptation?

Back 39

1. Atrophy
2. Hypertrophy
3. Hyperplasia
4. Metaplasia
5. Dysplacia

Front 40

Metaplasia

Back 40

the replacement of one adult cell type with another adult cell type

eg response to irritation resulting in a change from columnar to squamous cells in the RT

Front 41

Dysplasia

Back 41

-abnormal but non-neoplastic tissue development

-characterized by:
1. pleomorphism
2. hyperchromasia
3. increase in mitotic activity
4. loss of normal orientation

Front 42

pleomorphism

Back 42

range of sizes and shapes of the cells and their nuclei

Front 43

cloudy swelling

Back 43

-common first manifestation of injury in which cells swell w/ course granules in the cytoplasm

-loss of Na/K ATPase

Front 44

What are the 3 nuclear changes in necrosis?

Back 44

1. pyknosis
2. Karyolysis
3. Karyorrhexis

-cell death by necrosis invariably results in an inflamm response

Front 45

Pyknosis

Back 45

darkly stained and shrunken nuclei

Front 46

Karyolysis

Back 46

swollen and abnormally pale nuclei

Front 47

Karyorrhexis

Back 47

rupture and fragmentation of the nuclei

Front 48

Coagulative necrosis

Back 48

-basic architecture of the tissue is maintained
-tissue may appear fixed with a loss of cellular detail
-characteristic of hypoxic death in most tissues

Front 49

What are the 6 types of necroses?

Back 49

1. Coagulative necrosis
2. Liquifactive necrosis
3. Caseous necrosis
4. Fat necrosis
5. Gangrenous necrosis
6. Fibrinoid necrosis

Front 50

Liquifactive necrosis

Back 50

destruction of cells by hydrolytic enzyme digestion either from cells own lysosomes or exogenously from phagocytic cells
-occurs in abscesses in the brain

Front 51

Caseous necrosis

Back 51

-loss of tissue architecture w/out liqification
-tissue is replaced w/ a granular, soft, cheesy (caseous) material

-seen in TB

Front 52

Fat necrosis

Back 52

-not a specific pattern of necrosis
-focal areas of fat destruction from lipases released from acinar cells of the pancreas

Front 53

Gangrenous necrosis

Back 53

Not a specific pattern of necrosis

-describes ischemic necrosis of a limb
-basically coagulative necrosis w/ a liquefactive component

Front 54

Fibrinoid necrosis

Back 54

-Not a specific pattern of necrosis
-morphologic change in dead cells in which the tissue stains deeply eosinophilic, homogenous , refractile, resembling fibrin
-limited to small arteries, arterioles, venules, and glomerular vessels

Front 55

4 types of apoptosis in disease

Back 55

1. Cells infx w/ viruses (By T-lymphocytes and NK cells)
2. Modulation of CMI responses
3. Cells w/ DNA damage (increase production of p53 inducer of apop)
4. Radiation and chemicals used in cancer therapy

Front 56

What are 3 external signals (negative signals) that trigger apoptosis when activated?

Back 56

1. TNF-A binding to TNF receptor
2. Lymphotoxin (TNF-B) binding to TNF receptor
3. Fas ligand (Fas L) binding to Fas receptor

Front 57

The intrinsic or mitochondrial pathway of apoptosis

Back 57

-relative [] of 2 mito membrane proteins Bax and Bcl-2
-Bcl-2 inhibs the action of Bax--> cellular damage leads to an increase in [Bax]--> increase in permeability of the mito membrane allowing cytochrome c to leak out

Front 58

The intrinsic or mitochondrial pathway of apoptosis...Part 2

Back 58

released cytochrome c binds to protein Apaf-1--> aggregate to form apoptosomes--> bind to and activate a protease designated caspase-9-->activation of proteolytic enzymes that are involved in degradation of nuclear and cytoplasmi contents of cell

Front 59

Extrensis or death receptor pathway of apoptosis

Back 59

-Fas and TNF receptor activation transmits a signal to that cytoplasm that results in the activation of caspase-8--> initiates a cascade of caspases that activate enzymes--> cell degradation