Term
| In dying cells, phospholipids are lost from the cell membrane due to... |
|
Definition
| phospholipase activation (via Ca2+) and lack of synthesis of new membrane lipids. Also, breakdown products of membrane phospholipids, like fatty acids and lysophospholipids may accumulate, having a detergent effect on remaining membranes |
|
|
Term
| Dying myocardium releases what two easily measured intracellular molecules? |
|
Definition
| troponin and creatine kinase (CK) |
|
|
Term
| Dying hepatocytes release what two easily measured intracellular molecules? |
|
Definition
| ASpartate Transaminase (AST) and ALanine transaminase (ALT) |
|
|
Term
| Morphological changes of mitochondria indicative of irreversible cell injury include... |
|
Definition
| markedly swollen with large dense bodies containing Ca2+ |
|
|
Term
| Name three terms that describe different characteristic nuclear changes that occur with irreversible cell injury |
|
Definition
| karylolysis, Pyknosis, Karyorrhexis |
|
|
Term
|
Definition
| progressive disruption and random digestion of the nucleus and its components. The nucleus appears to "fade away" when viewed microscopically |
|
|
Term
|
Definition
| when chromatin becomes dense and shrinks (due in part to pH changes) |
|
|
Term
|
Definition
| When the chromatin of a pyknotic nuclei breaks up into smaller dense structures |
|
|
Term
| T/F Signs of irreversible cell damage can be detected with light microscopy before cell death has occured. |
|
Definition
| FALSE. Recognizable changes may not develop for 6 to 12 hours after cell death has already occurred |
|
|
Term
| What causes reperfusion injury? |
|
Definition
| generation of reactive oxygen species including oxygen derived free radicals that damage or kill cells that might have otherwise recovered from the ischemic insult |
|
|
Term
| What is the molecular formula of the superoxide anion? |
|
Definition
|
|
Term
| How are oxygen free radicals produced? |
|
Definition
| certain types of radiation can cause the hydrolysis of water, generating OH-. Also, enzymatic transformation of certain chemicals or toxins by cells can result in the formation of free radicals. |
|
|
Term
| Name normal mechanisms in the body which produce small amounts of free radicals. |
|
Definition
| oxidative phosphorylation, respiratory burst of neutrophils, and intracellular oxidases like xanthine oxidase |
|
|
Term
| The respiratory burst of neutrophils creates the free radical _______ via a certain enzyme called __________. |
|
Definition
| superoxide anion (O2-); NADPH oxidase |
|
|
Term
| How do iron and copper contribute to increased free radicals? |
|
Definition
| they serve as catalists for free radical formation (like in the fenton reaction) |
|
|
Term
| How do free radicals injure the cell membrane? |
|
Definition
| free radicals interact with double-bonds forming lipid peroxides. These are unstable and cause the loss of a H+ atom from adjascent unsaturated lipid molecules starting a cascade. Radical scavengers present in membrane normally stop this. |
|
|
Term
| What is the Fenton reaction? |
|
Definition
| Fe2+ reacts with H2O2 to form OH- |
|
|
Term
| How do free radicals harm proteins? |
|
Definition
| cause protein-protein cross-linkages or breaks in the backbone of the protein structure |
|
|
Term
| What do free radicals do to DNA? |
|
Definition
| cause single strand breaks |
|
|
Term
| What creates the free radicals that cause reperfusion injury? |
|
Definition
| 1) proteolysis during ischemia produces xanthine oxidase and xanthine dehydrogenase which is able to produce free radicals in the presence of O2. 2) neutrophils are activated to undergo respiratory burst |
|
|
Term
| Reaction by which Hypoxanthine produces free radicals. |
|
Definition
| Hypoxanthine +O2 +H2O --> Xanthine + H2O2 + O2- |
|
|
Term
| Reaction by which xanthine creates free radicals. |
|
Definition
| Xanthine + O2 + H20 --> Uric Acid + H2O2 + O2- |
|
|
Term
| How is Carbon tetrachloride (CCl4) harmful if swallowed while being nontoxic? |
|
Definition
| CCl4 is acted upon by the P450 enzymes of liver cells, generating a free radical (CCl3). Damage to rER inhibits protein synthesis leading to fatty liver and even cell necrosis |
|
|
Term
| How does the body prevent molecules like Fe and Cu from propogating free radicals? |
|
Definition
| By binding them to storage/transport proteins like transferrin and ferritin for Fe and Ceruloplasmic for Cu |
|
|
Term
| Name some enzymes that break down free radicals into less harmful substances. |
|
Definition
| catalase, superoxide dismutase, glutathione peroxidase |
|
|
Term
| After cell necrosis, the cell constituents are enzymatically digested. Where do the enzymes come from? |
|
Definition
| the cells own lysosomes (autolysis) or from inflammatory cells (heterolysis) |
|
|
Term
| Why does a necrotic cell become more eosinophilic? |
|
Definition
| ribosomes containing RNA disolve in the normally basophilic cytoplasm, and increased uptake of eosin by denatured proteins |
|
|
Term
|
Definition
| predominate type of necrosis where proteins are denatured more than cell components are digested. This means cell outlines and tissue architecture are preserved initially |
|
|
Term
| What is an infarct? What are the two types of infarcts? |
|
Definition
| an area of coagulation necrosis due to ischemia. 1) pale or anemic and 2) hemorrhagic or red |
|
|
Term
| Why are some infarcts hemorrhagic? |
|
Definition
| in organs with a dual blood supply (like the lung) or in which the loose nature of tissue allows the accumulation of blood (the gut) the infarcted area contains large amounts of red cells, giving a hemorrhagic appearance grossly, and lots of RBCs within tissues by light microscopy |
|
|
Term
|
Definition
| a special type of coagulation necrosis which is due to gradual ischemia. Can be dry or wet (wet means infected with bacteria) |
|
|
Term
| Name the type of necrosis that occurs in the brain. |
|
Definition
|
|
Term
| Why does necrosis due to bacterial infection become liquefactive necrosis? |
|
Definition
| bacteria degrade/liquify the dead tissue and neutrophils create pus via their granular content |
|
|
Term
| What organisms cause caseous necrosis? |
|
Definition
| mycobacterial and some fungi |
|
|
Term
| Discrete areas of caseous necrosis are called _________. |
|
Definition
|
|
Term
| T/F Apoptosis requires ATP. |
|
Definition
|
|
Term
|
Definition
| a protein that is produced in radiation damaged cells. It can arrest cell division and allow time for DNA to repair. If impossible to repair DNA, p53 causes cell to undergo apoptosis |
|
|
Term
|
Definition
| cysteine containing proteases which cleave at aspartate residues and result in cleavage of cytoskeletal proteins and nuclear scafolding |
|
|
Term
| Name the three types of caspases. |
|
Definition
| interleukin converteing enzyme (ICE)-like, death-signaling or initiator caspases, executioner or effector caspases |
|
|
Term
| Which caspases are initiator caspases? Which are effector caspases? |
|
Definition
| executioner- 3,6,7 initiator- 2,8,9 |
|
|
Term
|
Definition
| caspace-activated deoxyribonuclease. When caspase cleaves CAD's inhibitor protein, CAD cleaves DNA between the nucleosomes resulting in 180-200 bp fragments |
|
|
Term
| How do effector caspases causes the cell to make apoptotic bodies? |
|
Definition
| they activate a transglutaminase which cross-links cytoplasmic proteins to form a protein "shel" directly beneath the plasmalemma, which may be important in the fragmentation into apoptotic bodies |
|
|
Term
| How do phagocytic cells know to eat apoptotic bodies and not cause any inflammation? |
|
Definition
| effector caspases cause exposure of phosphatidyl serine which acts as a ligand for receptors on phagocytic cells to engulf the fragments and then secrete antiinflammatory cytokines |
|
|
Term
| Signals that induce apoptosis are... |
|
Definition
| 1) oxygen derived free radicals 2) damage to DNA3) binding of ligands to specific receptors like fas ligand to fas receptor or TNF alpha to TNFR1 |
|
|
Term
|
Definition
| outer mitochondrial membrane |
|
|
Term
| Molecules that affect the function of Bcl-2 include... |
|
Definition
| other members of the bcl-2 family like Bax and Bad (promote apoptosis) and Bcl-XL (inhibit apoptosis). As well as Apaf-1 which sequesters Bcl-2 from the cytoplasm |
|
|
Term
| What happens to Bcl-2 and Apaf-1 when there is damage to a cell? |
|
Definition
| Bcl-2 releases Apaf-1 into the cytoplasm and allows cytochrome c to escape from the mitochondria |
|
|
Term
| Name the structures that make up an apoptosome |
|
Definition
| apaf-1, cytochrome-c, and the zymogen procaspase-9 which then becomes active caspase 9 |
|
|
Term
|
Definition
| portion of death receptors that are intracellular |
|
|
Term
| What happsn when Fas ligand binds Fas receptor? |
|
Definition
| death domain of Fas tells FADD to activate procaspase-8 to caspase-8 which activates the executioner caspases |
|
|
Term
| What does FADD stand for? |
|
Definition
| Fas-associated death domain |
|
|
Term
| The death domain of TNFR1 binds to what adaptor protein? |
|
Definition
| TRADD (TNF Receptor-Associated Death Domain) |
|
|
Term
| What are the two different things TRADD can bind to? |
|
Definition
| 1) FAS 2) TRAF2 (TNF receptor associated factor 2) and RIP (receptor interacting protein) |
|
|
Term
| What happens when TRADD binds to TRAF2 and RIP? |
|
Definition
| promotes activates of transcription factors that translocate to the nucleus and activate survival genes which oppose apoptosis and promote inflamation |
|
|
Term
| Does TNF alpha most often cause apoptosis or inflammation? |
|
Definition
| inflamation; only when a cell is sensitized like by glutathione depeletion does it become apoptotic |
|
|
