Cell Injury Stress and Adaptations Flashcards

Question

Describe fat necrosis. What is it a result of and when does it classically occur?

Answer 1

a. Focal areas of fat destruction, resulting from trauma to fat b. Classically occurs in breast (trauma to breast tissue) or pancreas (release of pancreatic lipases into peritoneal cavity (pancreatitis)) c. Grossly visible chalky-white areas with saponification (due to calcium deposits)

Answer 2

Vascular damage due to deposition of antibodies/antigens on blood vessels Bright pink and amorphous appearance on H&E stain

Answer 3

cell "eats" its own contents to derive nutrients, mediated by delivery of cytoplasmic material to lysosomes Formation of phagophore and engulfment of contents -> formation of autophagosome -> maturation of autophagosome via fusion with lysosome + degradation of contents

Answer 4

- Implicated in exercise and aging, and other situations where there is a lack of nutrients - Prominent in cells undergoing atrophy - Can trigger cell death independent of apoptosis or necrosis

Answer 5

Cancer, neurodegenerative disorders, infectious diseases, IBD

Answer 6

Determinants: nature, duration, and severity of injury and (characteristics of injured cell) Consequences: type, state, and adaptability of cell

Answer 7

mitochondrial damage, membrane (PM and organelle) damage, DNA damage, and oxidative stress (free radicals and ROS)

Answer 8

Causes: Increased [Ca2+], ROS, hypoxia, chemical agents, defects in mitochondrial proteins (genetic mitochondrial diseases) Effects: 1) ATP depletion a) ↓ O2 -> ↓ oxidative phosphorylation -> ↓ ATP b) Impact of ↓ [ATP] i) Failure of Na+/K+ ATPase -> influx of Na+-> osmotic influx of water and cell swelling ii) ↑ [cAMP] -> ↑ phosphorylase/phosphofructokinase activity -> ↑ glycogenolysis/glycolysis -> rapid ↓ [glycogen] iii) Detachment of ribosomes from RER-> ↓ protein synthesis and ↑ misfolded proteins 2) Formation of ROS 3) Leakage of mitochondrial proteins -> initial step in intrinsic pathway of apoptosis -> cell death

Answer 9

Causes: 1) ROS 2) ↓ phospholipid synthesis accompanied by ↑ phospholipid breakdown 3) Cytoskeletal abnormalities a) Example: ↑ [Ca2+] -> activation of proteases that target cytoskeleton -> cytoskeletal breakdown, detachment of PM from cytoskeleton -> PM rupture/stretching Effects: 1) Mitochondrial membrane damage -> release of mitochondrial proteins 2) PM damage -> disruption of osmotic balance -> swelling of cells and loss of cell contents 3) Lysosomal membrane damage -> leakage of lysosomal enzymes -> diffuse lysis of cell components

Answer 10

Causes: Exposure to radiation, chemotherapy, ROS, spontaneous (esp due to aging) Effects: p53 activation-> apoptosis

Answer 11

Free radicals: chemical species w/a single unpaired electron in an outer orbit ROS: an oxygen-derived free radical

Answer 12

1) Redox reactions during normal metabolic processes, esp normal respiration 2) Absorption of radiant energy (UV, x-rays) 3) ROS generation by leukocytes during inflammation 4) Enzymatic metabolism of exogenous chemicals or drugs 5) Catalyzation of free radical formation by transition metals (ie Fe and Cu) 6) NO can act as a free radical

Answer 13

1) Antioxidants block free radical formation or inactivate free radicals (ie vitamin E, A, ascorbic acid) 2) Sequestration of Fe and Cu by transport and storage proteins 3) Enzymatic free radical scavengers: catalase, superoxidase dismutases, glutathione peroxidase Effects: can lead to either necrosis or apoptosis 1) Lipid peroxidation in membranes -> membrane damage 2) Oxidative modification of proteins -> formation of covalent cross-links, damage to active sites, disruption of conformation, ↑ proteasomal degradation 3) Formation of DNA lesions

Answer 14

Intracellular Ca2+ is much lower than extracellular, and is sequestered in mito + ER

Answer 15

Ischemia and toxins

Answer 16

They are not well understood, but potentially activation of metabolic enzymes in cytoplasm and mito

Answer 17

Causes: 1) Accumulation of misfolded proteins in ER 2) May be result of genetic abnormality in folding protein, viral infection that hacks protein synthesis machinery Effects: Unfolded protein response: ↑ chaperones, ↑ proteasome activity, reduced rate of protein translation 2) ER stress: If above efforts are not enough to cope, activation of caspases -> apoptosis

Answer 18

Ischemia is caused by hypoxia induced by reduced blood flow, most often caused by mechanical arterial obstruction i. There is no loss of blood flow in hypoxia, so anaerobic glycolysis can continue; in ischemia the loss of blood flow prevents any energy-producing metabolism (due to lack of nutrients), resulting in more rapid and severe cell/tissue damage

Answer 19

- Briefly, ischemia results in decreased ATP production and the subsequent effects (under mito damage) - Cell response: TF hypoxia-inducible factor-1 (HIF-1) -> angiogenesis, activation of cell survival pathways, ↑ glycolysis

Answer 20

Restoration of blood flow to ischemic tissue can lead to injury

Answer 21

i. Oxidative stress due to increased ROS and nitrogen species, resulting from leukocytes and damaged endothelial/parenchymal cells ii. Increased intracellular Ca2+ due to influx of Ca2+ through the damaged PM from the now perfused tissue iii. Inflammation due to release of "danger signals" by dead cells, cytokine release from resident macrophages, increased expression of adhesion molecules iv. Complement activation; IgM antibodies bind ischemic tissue -> complement binding upon reperfusion

Answer 22

increased size of cells --> increased size of organs

Answer 23

Physiologic: growth of uterus during pregnancy (due mainly to growth of smooth muscle cells) Pathologic: skeletal and cardiac muscle hypertrophy as a response to increased metabolic or mechanical demands, due to their limited capacity for regeneration --> ^^ in size of cells result of ^^ed protein synthesis and #of myofilaments

Answer 24

Mechanical sensors in cell detects increased demands -> activation of downstream signaling pathways -> ↑ growth factor synthesis and activation of TFs that stimulate muscle protein transcription

Answer 25

increased #of cells

Answer 26

mediated by hormones and growth factors; occurs when there is a need to ^^fx capacity of hormone sensitive organs or there is need for compensatory increase after damage or resection Ex. Proliferation of glandular epithelia in female breast during puberty/pregnancy, liver regeneration after donation, bone marrow

Answer 27

Often result of excessive/inappropriate actions of growth factors/hormones 2) Ex: BPH, inappropriate hyperplasia of endometrium following menstruation 3) Although pathologic hyperplasia increases risk of cancer and is often a characteristic, it is a distinct process

Answer 28

Growth-factor driven proliferation of mature cells

Answer 29

reduction in size of organ/tissue due to a decrease in cell size and/or number

Answer 30

Occurs commonly during normal development; atrophy of notochord and thryoglossal duct during embryogenesis

Answer 31

1) Disuse atrophy- due to decreased workload (ie skeletal muscle atrophy following immobilization of a limb in a cast) 2) Denervation atrophy- due to a loss of innervation in muscle cells 3) Diminished blood supply (ie brain atrophy in old age due to reduced blood supply secondary to atherosclerosis) 4) Inadequate nutrition- profound malnutrition results in use of skeletal muscle as source of nutrients 5) Loss of endocrine stimulation- many hormone-dependent organs will atrophy upon loss of endocrine stimulation 6) Pressure- compression of a tissue

Answer 32

Decreased protein synthesis and increased protein degradation (via ubiquitin-proteasome pathway); autophagy

Answer 33

reversible change of one differentiated cell type to another

Answer 34

Occurs in respiratory tract in response to chronic irritation (ie smoking) Increases durability of epithelium, but decreases capacity to clear debris due to loss of cilia

Answer 35

Barrett esophagus, induced by refluxed gastric acid

Answer 36

Formation of mesenchymal tissue in tissue that does not normally contain these cell types

Answer 37

- Re-programming of local tissue stem cells or colonization by adjacent, differentiated sites (does not result from change in phenotype of terminally differentiated cells) - Induced by signals from cytokines, growth factors, ECM proteins

Answer 38

i. Inadequate removal of molecules secondary to defects in transport ii. Accumulation of molecules as a result of abnormal folding, packaging, transport, or secretion iii. Failure to degrade a metabolite as a result of lysosomal abnormalities iv. Deposition of abnormal exogenous substances within cell

Answer 39

abnormal accumulation of triglycerides in parenchymal cells (ie fatty liver)

Answer 40

Atherosclerosis, xanthomas, cholesterolosis, and Niemann Pick disease

Answer 41

formation of cholesterol-containing lipid-vacuoles in smooth muscle cells of aorta and large arteries

Answer 42

intracellular accumulations of cholesterol in macrophages

Answer 43

accumulation of cholesterol-laden macrophages in gallbladder

Answer 44

lysosomal disease involving protein involved in cholesterol trafficking

Answer 45

rounded, eosinophilic droplets, vacuoles, | or aggregates

Answer 46

1) Reabsorption droplets in proximal renal tubules 2) Russell bodies- accumulation of normal cellular proteins that are overly synthesized, resulting in distended RER that creates large eosinophilic inclusions 3) Accumulation of cytoskeletal proteins (ie neurofibrillary tangles in Alzheimer's) 4) Aggregation of abnormal proteins

Answer 47

alteration w/in cells or ECM that gives homogenous, glassy pink appearance of tissue section--> result of accumulation of IC and EC hyaline

Answer 48

Formation of clear vacuoles in cytoplasm filled w/glycogen; Diabetes mellitus or glycogen storage disorders

Answer 49

exogenous and endogenous; exogenous: Carbon as an air pollutant can accumulate in alveoli Endogenous: 1) Lipofuscin- yellow-brown, finely granular pigment in cytoplasm; seen in cells undergoing slow, regressive changes 2) Melanin- brown-black pigment formed by oxidation of tyrosine to dihydroxyphenylalanine by tyrosinase 3) Hemosiderin- golden yellow-to-brown, granular, crystalline pigment in cytoplasm; storage of Fe

Answer 50

abnormal tissue deposition of calcium salts, as a result of hypercalcemia

Answer 51

i. ↑ PTH secretion ii. Resorption of bone tissue iii. Vitamin-D related disorders iv. Renal failure

Answer 52

Dystrophic and metastatic

Answer 53

Calcification of locally dying tissues; occurs in areas of necrosis (independent of type)

Answer 54

normal tissues in the presence of hypercalcemia

Answer 55

what caused the disease - either genetic or environmental | Ex. Cystic fibrosis is a genetic disease

Answer 56

sequence of molecular, biochemical, and cellular events that lead to the development of disease; explains how etiologies give rise to symptoms. Ex. a transporter defect in CF leads to accumulation of mucus in the lungs and other places

Answer 57

Ex. CF affected cells will look different

Answer 58

"trouble breathing" for the CF patient etc.

Answer 59

Loss of function, biochemical changes, and release of cytoplasmic enzymes

Answer 60

• Healthcare's Perspective of this issue “Disease … is a pathological process, most often physical… some deviation from a biological norm. There is an objectivity about disease which doctors are able to see, touch, measure, smell. Diseases are valued as the central facts in the medical view…

Answer 61

Individual Patient's Perspective “Illness … is a feeling, an experience of unhealth which is entirely personal, interior to the person of the patient. Often it accompanies disease, but... Sometimes illness exists where no disease can be found…”