Term
| what must an INJURED CELL be able to do to survive? |
|
Definition
| produce ENERGY and produce a BARRIER to hostile external environment |
|
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Term
| why are HYPERTROPHIC CELLS said to be growing and destroying simultaneously? |
|
Definition
| proteins useful to function expand while organelles or proteins less essential are flagged with ubiquitin and destroyed to make room for expanding components |
|
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Term
| in HYPERTROPHY, stimuli lead to what? |
|
Definition
-Adaptive cellular remodeling
-Increase protein production
-Facilitation of cell function
-Promotion of cell survival |
|
|
Term
| SUBCELLULAR HYPERTROPHY results from enlargement of what organelle? |
|
Definition
| smooth ER-detoxifies, some metabolism |
|
|
Term
| what is the mechanism of HYPERPLASIA? what elicits hyperplasia? |
|
Definition
| cells in G0 enter G1 and begin to divide, elicited by hormones, increased functional demands, or chronic injury |
|
|
Term
| what is ATROPHY? two types? |
|
Definition
| reduced size of organ or tissue due to decreased cell size and number, physiological and pathological |
|
|
Term
| what is METAPLASIA? example? |
|
Definition
| conversion of one cell type to another, BARRAT'S ESOPHAGUS |
|
|
Term
| what is the MECHANISM of METAPLASIA? |
|
Definition
| REPROGRAMMING of either STEM CELLS or MESENCHYMAL CELLS that result in new cell type |
|
|
Term
| what is DYSPLASIA? how does it differ from neoplasia? |
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Definition
| disordered growth and maturation of cellular components of tissue in epithelium- usually stay uniform in size *REVERSIBLE as long as stimulus is taken away |
|
|
Term
| characteristics of DYSPLASIA? |
|
Definition
| Pleomorphism, nuclear enlargement and irregularity, disarray in arrangement of epithelial cells |
|
|
Term
| what is HYDROPIC SWELLING? |
|
Definition
| Increase in cytoplasm with centrally located nuclei due to increased water content- acute, reversible, number of causes |
|
|
Term
| what is the MECHANISM of HYDROPIC SWELLING? |
|
Definition
| damage either to sodium pumps or ATP synthesis which directly affects sodium pumps which leads to water flow |
|
|
Term
| characteristics of NECROSIS? |
|
Definition
| exogenous stress causes ion imbalance and swelling via homeostasis disruption, little ATP production, INFLAMMATION- DIFFERENT FROM APOPTOSIS (PHAGOCYTOSIS) |
|
|
Term
| what is the characteristic CYTOPLASMIC finding in NECROSIS? why? |
|
Definition
| staining is more red than normal, disaggregation of ribosomes leads to more eosin binding sites=more red |
|
|
Term
| what are the characteristic NUCLEAR findings of NECROTIC cells? |
|
Definition
pyknosis - shrunken basophilic nucleus
karyorrhexis - fragmentation
karyolysis - extrusion or no of chromatin staining |
|
|
Term
| what is COAGULATIVE NECROSIS? example? |
|
Definition
| Light microscopic changes in a dead or dying cell whereby cellular outlines are still recognizable in early stages *GANGRENE |
|
|
Term
| what is LIQUIFACTIVE NECROSIS? |
|
Definition
| Rapid dissolution of cells most often due to release of neutrophil (polymorphonuclear cell) hydrolytic enzymes |
|
|
Term
| what is CASEOUS NECROSIS? how does it differ from COAGULATION NECROSIS? |
|
Definition
| "cheese-like", related to Tuberculosis and granulomatous inflammation, differs from coagulation necrosis in that fails to retain cellular outlines |
|
|
Term
| how does FAT NECROSIS appear histologically? mechanism? |
|
Definition
| little soap-like white areas which result from triglycerides which come from ruptured adiposites which are broken down into fatty acids and bind to calcium |
|
|
Term
| what is FIBRINOID NECROSIS? |
|
Definition
| seen in immune reactions associated with blood vessels, complexes and fibrin seen in vessel walls |
|
|
Term
| what are some MECHANISMS of CELL INJURY? |
|
Definition
| decreased ATP, Mitochondrial damage, Ca++ entry, increased reactive oxygen species, membrane damage, protein misfolding/DNA damage |
|
|
Term
| how does MITOCHONDRIAL INJURY lead to NECROSIS? APOPTOSIS? |
|
Definition
low oxygen decreases ox/phos and ATP production leads to NECROSIS
MPTP in membrane--> cytochrome c release--> APOPTOSIS |
|
|
Term
| what contributes to the accumulation of CALCIUM in the cell during cell injury? what does this cause? |
|
Definition
| influx of extracellular calcium + Ca released from damaged ER + Ca released from damaged mitochondria causes activation of ATPase, phospholipases, proteases, and endonucleases |
|
|
Term
| what are examples of REACTIVE OXYGEN SPECIES? |
|
Definition
|
|
Term
| what are sources of SUPEROXIDE (O2-)? causes? |
|
Definition
| leaks in mito ETC, part of inflammatory response-->both act to destroy phagocytosed material and signal intermediates that release proteolytic enzymes |
|
|
Term
| what is the SOURCE of HYDROGEN PEROXIDE? |
|
Definition
-Catabolism of superoxide by superoxide dismutase
-Produced directly by peroxisome oxidases
-->H2O2 is not very toxic on its own, but is used to make OH- by myeloperoxidase and fenton rxn |
|
|
Term
| what are SOURCES of HYDROXYL RADICAL? |
|
Definition
| Fenton Reaction (Fe+H2O2), Haber-Weiss Reaction (O2- + H+) Radiolysis |
|
|
Term
| what are ACTIONS of the HYDROXYL RADICAL? |
|
Definition
Lipid peroxidation-results in loss of membrane integrity
Protein interactions-Proteins fragment, cross-link, aggregate and degrade DNA strand breaks, modified bases, and cross-links |
|
|
Term
| what are examples of MISFOLDED PROTEIN DISEASES? |
|
Definition
| alpha1 antitrypsin deficiency, prion diseases, lewy bodies (alpha synuclein), neurofibrillary tangles (tau protein-alzheimers), mallory bodies (intermediate filaments-alcoholism) |
|
|
Term
| what are the two final outcomes of MISFOLDED PROTEINS? |
|
Definition
| cannot be incorporated into correct site--> DEGRADATION, form TOXIC AGGREGATION (alzheimers and parkinsons) |
|
|
Term
| what are the effects of REPERFUSION in SHORT TERM ISCHEMIC EVENTS? LONG TERM? |
|
Definition
short term- reperfusion completely restores cellular integrity
long term-reperfusion is destructive |
|
|
Term
| RADIATION causes the formation of what oxide radical? |
|
Definition
|
|
Term
| LOWER DOSES (300-1000R) of radiation undergo what mechanism of cell damage? HIGHER DOSES(>2000)? |
|
Definition
LOWER-produces OH- which damages labile cells -->APOPTOSIS
HIGHER-->NECROSIS |
|
|
Term
| what are the two MECHANISMS by which viruses kill cells? |
|
Definition
DIRECTLY (nutrient depletion and induced apoptosis)
VIA IMMUNOLOGICAL INTERMEDIATES (compliment, antibodies, granzymes, etc) |
|
|
Term
| CHEMICALLY mediated cell injury usually leads to what outcome? examples? |
|
Definition
| necrosis, Carbon Tetrachloride and acetaminophen |
|
|
Term
| what is the GROSS MORPHOLOGY of an APOPTOTIC cell? |
|
Definition
-Nuclear condensation and fragmentation
-Segregation of organelles into distinct regions
-Blebs of cellular membrane
-Membrane bound cellular fragments which often have no nuclear material
-No inflammatory response, only phagocytosis |
|
|
Term
| what is the DEVELOPMENTAL and HOUSEKEEPING role of APOPTOSIS? |
|
Definition
1. fetal development-regression of anatomical features
2. elimination of OBSOLESCENT cells
3. elimination of MUTATED or INFECTED CELLS |
|
|
Term
| what are the three ways that APOPTOSIS is initiated in cells? |
|
Definition
Intrinsic pathway - via mitochondria
Extrinsic pathway - via death receptor converting procaspases into active caspases
Cell mediated - via granzymes |
|
|
Term
| what are methods of detecting APOPTOSIS? |
|
Definition
-Nucleosomal Laddering – Cleavage of chromosomal DNA by endonucleases in a very specific pattern
-TUNEL – Terminal deoxyribonucleotidyl transferase (TdT) transfers a fluorescent nucleotide to expose breakpoints in DNA
-Activation of caspases
-Membrane alterations |
|
|
Term
| when faced with CHANGE IN ENVIRONMENT, what are the two possible outcomes of the cell? |
|
Definition
Irreversible injury leading to death
Reversible injury leading to adaptation |
|
|
Term
| if a cell adapts in the face of changes to the environment, what changes will result? |
|
Definition
-Conservation of resources
-Decreasing or ceasing differentiated properties
-Focus on cell survival
*Adaptations e.g. atrophy, hypertrophy, hyperplasia etc. |
|
|
Term
| what does IRREVERSIBLE CELL INJURY lead to? |
|
Definition
|
|
Term
what type of CELLULAR RESPONSE will be elicited by:
-increased demand or stimulus
-decreased nutrition or stimulus
-chronic irritation |
|
Definition
| hypertrophy, atrophy, metaplasia |
|
|
Term
| what are cellular mechanism to maintain HOMEOSTASIS? |
|
Definition
1. PROTEOSOMES - ubiquitin
2. chaparone mediated autophagy |
|
|
Term
| examples of cellular MORPHOLOGICAL ADAPTATIONS to injury? |
|
Definition
| hypertrophy, atrophy, hyperplasia, metaplasia, dysplasia, etc. |
|
|
Term
| what is the MECHANISM of CELL ATROPHY? |
|
Definition
| protein synthesis is decreases, degradation increases, change in gene expression, activation of the ubiquitin pathway |
|
|
Term
| when does recognizable cell injury occur? |
|
Definition
| when environmental changes exceed the cells ability to maintain homeostasis |
|
|
Term
| what is PHYSIOLOGIC cell death? PATHOLOGIC cell death? |
|
Definition
physiological-apoptosis
pathological-necrosis |
|
|
Term
| describe the characteristics of misfolded protein aggregation? |
|
Definition
-take on a BETA PLETED configuration in place of random coils or alpha helical configuration
-form amyloids and produce cell injury |
|
|
Term
| what is the MECHANISM of ISCHEMIC INJURY? |
|
Definition
| oxygen deprivation--> switch from AEROBIC TO ANAEROBIC METABOLISM--> less ATP production -->less cellular energy for metabolism including maintenance of gradient between external and internal compartments |
|
|
Term
| why is REPERFUSION after an ISCHEMIC INJURY dangerous? players other than NEUTROPHILS? |
|
Definition
back up of blood includes back up of NEUTROPHILS and other intermediates that could release ROS-->greater damage than before (still want to reperfuse anyway)
XANTHINE OXIDASE, NITRIC OXIDE |
|
|
Term
| what are the general effects of INFLAMMATORY CYTOKINES? |
|
Definition
-Promote vasoconstriction
-Stimulate cellular adherence e.g. platelets and neutrophils |
|
|
Term
|
Definition
| collections of CHOLESTEROL in FOAMY CELLS |
|
|
Term
|
Definition
1. too much fat coming into liver (diabetes, starvation)
2. not functioning metabolic pathways (alcoholism)
3. decreased apoprotein availability (decreased protein production) |
|
|
Term
| what does HYPERPROTEINURIA cause? |
|
Definition
| causes HYALINE DROPLETS in proximal convoluted tubule as protein is reabsorbed |
|
|
Term
| what is the result of protein aggregation in a plasma cell? what causes this? |
|
Definition
| RUSSELL BODY, due to antibodies being produced at very high rates |
|
|
Term
|
Definition
| indigestible cross linked proteins that accumulate mainly in terminally differentiated cells e.g. neurons and myocardial cells ± hepatocytes |
|
|
Term
|
Definition
| insoluble brown-black pigment found principally in epidermal cells of skin and eye-made from TYROSINE, protects against UV |
|
|
Term
| what are examples of EXOGENOUS PIGMENTS? |
|
Definition
| TATTOOS, ANTHRACOSIS-storage of carbon particles in macrophages |
|
|
Term
| what are the INTRACELLULAR STORAGE PROTEINS associated with IRON accumulation? |
|
Definition
|
|
Term
| what increases total body iron? what is the heritable form of iron overload? |
|
Definition
increased intestinal absorption, transfusions
HEMOCHROMATOSIS |
|
|
Term
| where do we see abnormalities of GLYCOGEN STORAGE? |
|
Definition
-Inherited impairment or absence of glycogen degradation enzymes
-Hyperglycemia due to uncontrolled diabetes mellitus |
|
|
Term
| what are LYSOSOMAL STORAGE DISEASES associated with? |
|
Definition
| associated with breakdown products of COMPLEX LIPIDS and MUCOPOLYSACCHARIDES |
|
|
Term
|
Definition
| generic morphologic descriptor used to describe material that has a red, amorphous, homogenous appearance when stained with H &E |
|
|
Term
| what is DYSTROPHIC CALCIFICATION? |
|
Definition
| Macroscopic deposition of calcium salts in injured tissues, depositions come from extracellular sources and are sand like or even harder |
|
|
Term
| what is METASTATIC CALCIFICATION? |
|
Definition
| DERANGED CALCIUM METABOLISM caused by virtually any disorder causing hypercalcemia |
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