Shared Flashcard Set

Details

Irreversible Cell Injury and Necrosis
8.3 at 8:30am by Dr. Vander Heide
55
Pathology
08/03/2011

Additional Pathology Flashcards

 


 

Cards

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
Karyloysis
Definition
progressive disruption and random digestion of the nucleus and its components. The nucleus appears to "fade away" when viewed microscopically
Term
Pyknosis
Definition
when chromatin becomes dense and shrinks (due in part to pH changes)
Term
Karyorrhexis
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
O2-
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
Coagulation necrosis
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
What is gangrene?
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
Liquefactive necrosis
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
granulomas
Term
T/F Apoptosis requires ATP.
Definition
true
Term
What is p53?
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
What are Caspases?
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
CAD
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
Where is Bcl-2 found?
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
What are death domains?
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