Pb&t Cellular Pathology & Inflammation

Front 1

Mechanisms of atrophy?

Back 1

1. Increased rate of protein degradation, 2. Increased number of autophagic vacuoles.

Front 2

How is protein degradation increased?

Back 2

1. lysosomal enzymes degrade proteins, 2. ubiquitin-proteasome pathway.

Front 3

How does the ubiquitin-proteasome pathway work?

Back 3

cytosolic & nuclear proteins conjugated w/ubiquitin, then degraded w/in proteasome.

Front 4

What are residual bodies?

Back 4

undigested organelles persisting w/in autophagic vacuoles (e.g., lipofuscin granules)

Front 5

What & where is squamous metaplasia? Side effects?

Back 5

columnar to squamous epithelium in bronchial epithelium (cigarette smokers). Loss of mucus production, potential for dysplasia & carcinoma.

Front 6

What & where is columnar metaplasia? Side effects?

Back 6

squamous to columnar epithelium in lower esophagus of patients w/chronic acid reflux. Potential for dysplasia & carcinoma.

Front 7

What is pyknosis?

Back 7

condensation of nuclear chromatin. May be reversible or irreversible.

Front 8

What is karyorrhexis?

Back 8

fragmentation of nucleus. Probably irreversible.

Front 9

What is karyolysis?

Back 9

dissolution of nucleus. Cell death.

Front 10

What is hypoxia?

Back 10

oxygen deprivation.

Front 11

What is ischemia?

Back 11

decreased delivery of blood; most common cause of hypoxia.

Front 12

What are the biochemical mechanisms of cell injury?

Back 12

decreased ATP, membrane damage, increased intracellular Ca++, Reactive Oxygen Species

Front 13

What is mitrochondrial permeability transition (MPT)?

Back 13

Leakage of cytochrome c from mitochondria into cytosol d/t mito membrane damage. Leads to apoptosis.

Front 14

What happens with increased cytosolic Ca++?

Back 14

decreased ATP, decreased phospholips, disruption of membrane & cytoskeletal proteins, & activation of endonucleases (chromatin damage).

Front 15

What are 3 major antioxidant enzymes?

Back 15

superoxide dismutase, catalase, & glutathione peroxidase

Front 16

How are free radicals removed?

Back 16

spontaneous decay, antioxidants, & binding of metal ions to minimize OH formation (ferritin stores Fe; ceruloplasmin stores & transports Cu).

Front 17

Two consistent features of irreversible cell injury?

Back 17

inability to fix or reverse mitochondrial dysfunction & severely disrupted membrane functions.

Front 18

Why are troponin & CK-MB used to diagnose cell death?

Back 18

They are intracellular proteins that enter into systemic circulation when their cell's PM is no longer intact. Diagnose MI.

Front 19

Examples of reversible cell injury?

Back 19

hydropic degeneration, macrovesicular steatosis, intercellular edema, inflammation (eosinophils present).

Front 20

What is coagulation necrosis?

Back 20

most common type of necrosis. typical of hypoxia-mediated cell death. Proteins denatured & coagulate. Gradual nuclear degeneration. "Ghost Cells"

Front 21

What is liquefactive necrosis?

Back 21

complete enzymatic digestion of cells; transforms tissue into viscous mass. Hypoxic death of CNS cells; infxns w/severe inflammation &/or toxin elaboration

Front 22

What is gangrenous necrosis?

Back 22

dry: no superimposed infection. wet: with superimposed infection (often sepsis). Describes clinically distinctive gross appearance. Coagulation necrosis.

Front 23

What is caseous necrosis?

Back 23

a form of coagulation necrosis; "cheesy" gross appearance. Seen in TB, certain fungal infxns. Caseating granuloma.

Front 24

What diseases cause caseating granulomas?

Back 24

mycobacteria, fungi

Front 25

Diseases that cause non-caseating granulomas?

Back 25

foreign materials, hypersensitivity rxns, sarcoidosis, leprosy, Bartonella sp.

Front 26

Where is fat necrosis seen?

Back 26

pancreas - d/t drinking binge, blockage d/t gallstones

Front 27

How is intrinsic apoptosis initiated?

Back 27

withdrawal of growth factors & hormones

Front 28

How is extrinsic apoptosis initiated?

Back 28

receptor-ligand interactions: FAS & TNF-receptors

Front 29

Function of Bcl-2?

Back 29

inhibits apoptosis by (1) directly preventing release of cytochrome c & (2) binding to & sequestering pro-apoptotic protease activating factor (Apaf-1)

Front 30

What is atherosclerosis?

Back 30

accumulation of cholesterol within macrophages in intimal layer of large arteries w/associated fibrosis

Front 31

What is xanthoma?

Back 31

accumulation of cholesterol w/in macrophages of dermis or tendons in pts w/hypercholesterolemia

Front 32

What is cholesterolosis?

Back 32

accumulation of cholesterol w/in macrophages of laminapropria of galbladder.

Front 33

Match pigment to disease:
1. lipofuscin
2. anthracosis
3. hemosiderin
4. homogentistic acid

Back 33

1. just aging & lipid peroxidation
2. usually mild; nodular fibrosis; pneumoconiosis
3. hemochromatosis
4. ochronosis/alkaptonuria

Front 34

What is dystrophic calcification?

Back 34

local deposition of calcium salts in nonviable (dead/damaged) tissue despite normal serum calcium level. (e.g., calcific aortic stenosis)

Front 35

What is metastatic calcification?

Back 35

deposition of calcium salts in normal, viable tissues; secondary to hypercalcemia

Front 36

Major causes of metastatic calcification?

Back 36

1. excess PTH (hyperparathyroidism or malignant neoplasm)
2. destruction of bone (tumors, cancer, Paget's disease)
3. vitamin D disorders (toxicity, sarcoidosis)
4. renal failure (retain phosphte)

Front 37

What is hyaline change?

Back 37

homogeneous pink, glass material either intralcellular or extracellular; seen in alcoholic hepatitis (Mallory bodies)

Front 38

What does EGF/TGF-alpha do?

Back 38

binds to EGF receptor family (tyrosine kinase activity): ERB B1 [proliferation of epithelia, fibroblasts, hepatocytes]
ERB B2 (HER-2) overexpressed in some Breast Ca

Front 39

What does PDGF do?

Back 39

migration & proliferation of fibroblasts, smooth muscle cells, monocytes, & hepatic stellate cells

Front 40

What does FGF do?

Back 40

macrophage, fibroblast, & endothelial migration (wound repair); angiogenesis; hematopoiesis

Front 41

What does VEGF do?

Back 41

promote vasculogenesis & angiogenesis

Front 42

What does TGF-beta do?

Back 42

pleotropic according to tissue:
1. normally inhibits epithelial & lymphocyte
proliferation
2. stimulates fibrogenesis & fibrosis in chronic inflammatory disorders

Front 43

Name important signal transducers that regulate cell growth:

Back 43

MAP-kinase, PI-3-kinase, IP3, cAMP, JAK/STAT

Front 44

Signal transduction systems that have intrinsic tyrosine kinase activity?
What happens?

Back 44

PI3, MAP-kinase, & IP3 pathways.
Receptor dimerizes & autophosphorylates.
G0 cells enter cell cycle

Front 45

Which pathway uses G-protein-coupled receptors?

Back 45

cAMP

Front 46

What are products of growth-promoting genes?

Back 46

c-MYC, c-JUN

Front 47

What are products of cell-cycle-inhibiting genes?

Back 47

p53

Front 48

What is scurvy & what causes it?

Back 48

bleeding from inadequately supported capillaries & venules.
vit C deficiency (can't hydroxylate procollagen)

Front 49

What causes bowing (children) & softening (adults) of bones?

Back 49

vitamin D deficiency

Front 50

What causes diarrhea d/t atrophy of columnar epithelium & scaling dermatitis?

Back 50

niacin deficiency

Front 51

What causes impaired night vision & dry eyes?

Back 51

vitamin A deficiency

Front 52

Name macromolecules in ECM.

Back 52

fibrous structural proteins (collagen & elastin), adhesive glycoproteins (fibronectin & laminin), & gel proteins (proteoglycans, hyaluronan)

Front 53

What is Ehlers-Danlos Syndrome (very brief)?

Back 53

problem w/type i, III, or IV collagen.

Front 54

Where is type IV collagen found?

Back 54

basemen membranes

Front 55

What is Marfan Syndrome?

Back 55

genetic defect in fibrillin; affects CV system (dissecting aorta), skeletal system, lens of eye

Front 56

What is fibronectin & its function?

Back 56

adhesive matrix glycoprotein; binds to cells & matrix proteins

Front 57

What is laminin & its function?

Back 57

most abundant adhesive matrix glycoprotein in basement membrane; forms polymers w/collagen type IV

Front 58

What are integrins & function?

Back 58

cell surface receptors.
1. attach cells to ECM proteins
2. attach cells to cells
3. form focal adhesion complexes w/cytoskeletal proteins. trigger signal transduction pathways.

Front 59

Steps in tissue repair by fibrosis?

Back 59

1. inflammation (0-6 days)
2. proliferation/migration of parenchymal & CT cells (4-14 days)
3. angiogenesis
4. synthesis of ECM proteins & collagen deposition
5. tissue remodeling
6. wound contraction
7. gradual acquisition of woulnd tensile strength

Front 60

Waht stimulates proliferation in tissue repair?

Back 60

TGF-beta, EGF, FGF, IL-1, TNF (secreted by macrophages, activated endothelial cells, platelets)

Front 61

Functions of TGF-beta in fibrosis?

Back 61

migration & proliferation of fibroblasts; increased colagen & fibronectin synthesis; decreases degradation of ECM by metalloproteinases.

Front 62

3 phases of tissue repair?

Back 62

1. emigration & proliferation of fibroblasts
2. deposition of ECM
3. maturation & remodeling

Front 63

What stimulates ECM remodeling by metalloproteinases?

Back 63

PDGF, EGF, IL-1, TNF

Front 64

What are matrix metalloproteinases?
How are precursors activated?

Back 64

enzyme familty that degrades ECM components.
activated by plasmin.

Front 65

What are TIMPs?
Made by what?

Back 65

tissue inhibitors of metalloproteinases.
made by mesenchymal cells.

Front 66

What are local factors which influence wound healing?
Which is most important?

Back 66

Infection (most important)
Mechanical factors
Foreign bodies
Location

Front 67

What are systemic factors which influence wound healing?

Back 67

Nutrition (profound effect)
Metabolic status
Circulatory status
Hormones, especially steroids

Front 68

What is keloid?

Back 68

hypertrophic scar; excess deposition of abnormally thick bunles of collagen in dermis.
African-Americans predisposed.