Term
| What is seen microscopically with hyaline change? |
|
Definition
| smooth, pink tissue appearance with H&E stain |
|
|
Term
| What causes the smooth pink tissue appearance in H&E with hyaline change? |
|
Definition
| excessive protein deposition |
|
|
Term
| What are 2 examples of intracellular hyaline changes? |
|
Definition
Russell bodies in plasma cells
alcoholic hyalin in hepatocyes |
|
|
Term
|
Definition
|
|
Term
|
Definition
| aggregates of intermediate filaments (mostly keratin) |
|
|
Term
| What are 3 examples of extracellular hyaline change? |
|
Definition
collagen in long-standing injury
amyloid deposits
thickened basement membrane in DM |
|
|
Term
|
Definition
| any alteration within cells or in the extracellular spaces or structures that gives a homogeneous, glassy pink appearance in tissue sections stained with H&E |
|
|
Term
| What are the 2 ways ATP can be synthesized? |
|
Definition
Aerobic oxidative phosphorylation
Anaerobic glycolysis |
|
|
Term
def
Aerobic oxidative phosphorylation |
|
Definition
| efficient production of ATP via mitochondrial ETC |
|
|
Term
|
Definition
| inefficient production of ATP via the metabolism of glucose |
|
|
Term
| What is the most common causative mechanism of ATP depletion? |
|
Definition
| decreased O2 availability |
|
|
Term
| What are the 3 causes of decreased O2 availability? |
|
Definition
1) hypoxia
2) *ischemia
3) deleterious cellular rxns |
|
|
Term
|
Definition
| decreased systemic O2 due to any etiology |
|
|
Term
| What are the 3 etiologies of hypoxia? |
|
Definition
1) decreased oxygenation of the blood (decreased hemoglobin levels)
2) decreased oxygen-carrying capacity of the blood (decreased oxygenation of hemoglobin)
3) ischemia |
|
|
Term
| When will you see decreased oxygenation of the blood? |
|
Definition
| resp. disorders or heart failure |
|
|
Term
| When will you see decreased oxygen-carrying capacity of blood? |
|
Definition
| severe anemia or carbon monoxide poisoning |
|
|
Term
|
Definition
| decreased blood flow to a tissue/organ |
|
|
Term
| What are the 3 consequences of ischemia? |
|
Definition
1) Hypoxia
2) dcreased supply of nutrients
3) decreased removal of toxic metabolic end-products |
|
|
Term
| What are the 4 deleterious cellular rxns caused by decreased ATP? |
|
Definition
| 1) decreased function of Na+/K+ pump
2) increased anaerobic glycolysis
3) decreased function of membrane-associated Ca2+ pump
4) loss of integrity of the rER |
|
|
Term
| What does decreased function of plasma membrane N+/K+ pump cause? |
|
Definition
| increased intracellular Na+ & H2O |
|
|
Term
| What does increased anaerobic glycolysis cause? |
|
Definition
| increased production of lactic acid => decreased intracellular pH |
|
|
Term
| What does decreased function of the membrane of the membrane-associated Ca2+ pump cause? |
|
Definition
| influx of Ca2+ => activation of numerous intracellular enzymes |
|
|
Term
| What does decreased function of the membrane of the membrane-associated Ca2+ pump cause? |
|
Definition
| influx of Ca2+ => activation of numerous intracellular enzymes |
|
|
Term
| What does loss of integrity of rER cause? |
|
Definition
| decreased and abnormal protein synthesis |
|
|
Term
| What is the normal ratio of cytosolic:extracellular [Ca2+]? |
|
Definition
|
|
Term
| What can cause an increase in cytosolic Ca2+? |
|
Definition
| 1) decreased activity of membrane-associated Ca2+ pump
2) increased permeability of subcellular & plasma membranes |
|
|
Term
| What numerous intracellular enzymes can be activated by increased intracellular Ca2+? |
|
Definition
1) ATPases
2) phospholipases
3) proteases
4) endonucleases |
|
|
Term
|
Definition
|
|
Term
|
Definition
| increased subcellular and plasma membrane permeability |
|
|
Term
|
Definition
| degradation of stuctural proteins |
|
|
Term
|
Definition
|
|
Term
|
Definition
| highly reactive molecules with an unpaired e- |
|
|
Term
| What are the 4 common causes on free radicals? |
|
Definition
1) aerobic oxidation
2) exposure to ionizing radiation
3) drug/toxin metabolism
4) neutrophil activation |
|
|
Term
| What are the body's 4 protective mechanisms against free radicals? |
|
Definition
| 1) enzymatic inactivation of O2-·
2) enzymatic breakdown of H2O2
3) antioxidants
4) iron- & copper- binding proteins |
|
|
Term
| What 2 enzymes does the body have to catalyze breakdown of H2O2? |
|
Definition
1) catalase
2) glutathione peroxidase |
|
|
Term
| What are the 3 deleterious cellular rxns caused by free radicals? |
|
Definition
1) lipid peroxidation of plasma & subcellular membranes
2) protein alteration & degradation
3) DNA damage
*propagation of autocatalytic chain of rxns |
|
|
Term
| What can cause mitochondrial injury? |
|
Definition
| activation of Ca2+-dependent intracellular enzymes or free-radical damage |
|
|
Term
| What 3 deleterious cellular rxns are caused by mitochondrial injury? |
|
Definition
1) decreased ATP
2) loss of membrane potential => inability to produce ATP => necrosis
3) escape of cytochrome c into cytosol |
|
|
Term
| What happens when cytochrome c escapes to the cytosol? |
|
Definition
|
|
Term
| What can cause cellular & subcellular membrane damage? |
|
Definition
| 1) decrease synthesis due to mitochondrial injury
2) increased degradation dur to phospholipase activation by increased cytosolic Ca2+
3) accumulation of phospholipid breakdown products
4) lipid peroxidation due to ROS
5) loss of cytoskeletal framework due to protease activity
6) direct lysis |
|
|
Term
| What 3 deleterious cellular rxns can occur due to cellular & subcellular membrane damage? |
|
Definition
| 1) mitochondrial membrane injury =>
a) loss of membrane potential => necrosis
b) escape of cytochrome c => apoptosis
2) plasma membrane injury => influx of Ca2+ & H2O and leakage of cellular contents
3) lysosomal membrane injury => release & activation of lytic enzymes |
|
|
Term
| What are the 3 types of cellular death & injury? |
|
Definition
1) *Hypoxia
2) Ischemia
3) Chemical injury |
|
|
Term
| What can cause hypoxic ischemia? |
|
Definition
Arterial or venous obstruction
severe hypotension |
|
|
Term
| What does the everity of cellular consequences of hypoxia depend on? |
|
Definition
| duration & particular cell type vulnerability |
|
|
Term
| Why does hypoxia due to ischema cause a greater degree of cellular damage than other causes of hypoxia? |
|
Definition
| decreased availability of glycolytic substrates and decreased removal of metabolic byproducts. |
|
|
Term
| Why is atrophy seen in hypoxia? |
|
Definition
| response due to decreased metabolic requirements in order to balance the oxygen supply |
|
|
Term
| What cellular injury caused by hypoxia is reversible? |
|
Definition
| decreased phosphorylation & ATP formation => decreased protein synthesis & Na+/K+ pump function => influx of Na+ & H2O => swelling => decreased cell function |
|
|
Term
| What cellular injury caused by hypoxia is irreversible? |
|
Definition
| decreased phospholipid synthesis & Ca2+ pump failure => influx of Ca2+ => Ca2+ damage => lysis of the lysosomes => irreparable damage to mitochondria => cell death (necrosis) |
|
|
Term
|
Definition
| exacerbation of ischemic cellular damage after restoration of blood flow to an area |
|
|
Term
| What are the 3 causes of reperfusion injury? |
|
Definition
1) *increased production of ROS
2) influx of leukocytes (mainly neutrophils)
3) activation of complement after Ab deposition |
|
|
Term
| How can chemical injury occur? |
|
Definition
Direct toxicity
Toxicity due to metabolic byproducts |
|
|
Term
| What metabolizes CCl4 to CCl3·? |
|
Definition
|
|
Term
|
Definition
| autocatalytic lipid peroxidation => rER damage & mitochondrial & plasma membrane damage |
|
|
Term
| What happens once CCl3· leads to rER damage? |
|
Definition
| decreased protein synthesis (including apoprotein) => decreased triglyceride export => fatty liver |
|
|
Term
| What happens once CCl3· leads to mitochondrial & plasma membrane damage? |
|
Definition
| increased membrane permeability & cytosolic Ca2+ => cell death |
|
|
Term
| When may cell injury not be apparent morphologically? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What can cause cellular swelling? |
|
Definition
| 1) plasma membrane damage => increased permeability => influx of Na+ & H2O
2) if ischemia
a) decreased blood flow => decreased O2 => decreased ATP => failure of Na+/K+ pump => influx of Na+ & H2O
b) increased cytosolic [osmotic] => influx of H2O |
|
|
Term
| What gross changes are seen in a organ with cellular swelling? |
|
Definition
|
|
Term
| What microscopic changes are seen in swollen cells? |
|
Definition
| enlarged cells with pale/clear cytoplasm |
|
|
Term
| What EM changes are seen in swollen cells? |
|
Definition
| cell surface blebs and distended mitochondria & ER |
|
|
Term
| What organ can have fatty change? |
|
Definition
|
|
Term
| What causes fatty deposits? |
|
Definition
| injury to ER => decreased protein synthesis => decreased lipid export => intracellular accumulation of fat |
|
|
Term
| What is seen microscopically in a fatty infiltration? |
|
Definition
| cytoplasmic lipid vacuoles. |
|
|
Term
| What are the 2 types of irreversible cell injury? |
|
Definition
|
|
Term
| Is necrosis or apoptosis always pathogenic? |
|
Definition
|
|
Term
|
Definition
| enzymatic digestion & leakage of cellular contents |
|
|
Term
| What is a key role in cellular & subcellular membrane damage due to Ca2+ influx? |
|
Definition
|
|
Term
| What are the 4 pathogenic causes of necrosis? |
|
Definition
1) plasma membrane: loss of cytosolic substrates
2) mitochondria: decreaed ATP
3) ER: decreased protein synthesis
4) lysosomes: release & activation of acid hydrolases => autolysis |
|
|
Term
| What cytoplasmic changes are seen in necrosis? |
|
Definition
1) increased eosinophilia
2) dense, clumped, irregular appearance |
|
|
Term
| What causes increased eosinophilia of cytoplasm in necrosis? |
|
Definition
1) decreased pH
2) decreased RNA
3) denatured proteins |
|
|
Term
| What causes the dense, clumped, irregular appearance of the cytoplasm in necrosis? |
|
Definition
1) decreased glycogen
2) disrupted cytoskeleton |
|
|
Term
| What causes nuclear changes in necrosis? |
|
Definition
| activated lysosomal enzymes & decreased pH (ultimately complete loss of nuclei) |
|
|
Term
| What are the 3 types of nuclear change that can be seen in necrosis? |
|
Definition
1) karyolysis
2) pyknosis
3) karyorrhexis |
|
|
Term
|
Definition
| fading of nuclear chromatin due to DNases |
|
|
Term
|
Definition
| nuclear condensation & shrinkage |
|
|
Term
|
Definition
|
|
Term
| Where does necrosis often surround? |
|
Definition
| host inflammatory response |
|
|
Term
| What ultrastructural changes are seen in necrosis? |
|
Definition
1) myelin figures
2) membrane disruption
3) amorphous intracellular debris |
|
|
Term
| What can help determine the etiology of necrosis? |
|
Definition
| specific morphologic patterns |
|
|
Term
| What ultimately happens to all areas of necrosis? |
|
Definition
| enzymatic degradation & phagocytosis by leukocytes |
|
|
Term
| What are the 5 types of necrosis? |
|
Definition
1) coagulative
2)liquefactive
3)caseous
4)fat
5)fibrinoid |
|
|
Term
| What are the 5 types of necrosis? |
|
Definition
1) coagulative
2)liquefactive
3)caseous
4)fat
5)fibrinoid |
|
|
Term
|
Definition
|
|
Term
| What causes coagulative necrosis? |
|
Definition
| hypoxia/ischemia (not in brain) => denaturation of enzymatic & structural proteins => delayed proteolysis |
|
|
Term
| What is seen in coagulative necrosis microscopically? |
|
Definition
| initial preservation of the tissue architecture (pink, ghost, cellular remnants with structural outlines intact) |
|
|
Term
| What are 3 examples of coagulative necrosis? |
|
Definition
1) MI
2) renal infarct
3) dry gangrene |
|
|
Term
| What causes liquefactive necrosis? |
|
Definition
hypoxia/ishemia (brain only)
usually pyogenic bacterial inf. => imflammation => WBC lysosomal enzyme release => enzymatic digestion & liquefaction of tissue |
|
|
Term
| What is seen microscopically in liquefactive necrosis? |
|
Definition
| focal loss of tissue architecture which is replaced by cellular debris & inflammatory cells |
|
|
Term
| What are 3 examples of liquefactive necrosis? |
|
Definition
1) abscess
2) cerebral infarct
3) wet gangrene |
|
|
Term
| What causes caseous necrosis? |
|
Definition
| mycobacterial and fungal inf. => activated macrophages & T cells => granulomatous inflammation with caseous (central) necrosis |
|
|
Term
| What is the gross appearance of caseous necrosis? |
|
Definition
| Caseous - crumbly, white & cheesy |
|
|
Term
| What is seen microscopically in caseous necrosis? |
|
Definition
| focal loss of cellular architecture & replacement by pink amorphous debris surrounded by a rim of plump epithelioid macrophages & lymphocytes |
|
|
Term
| What are 2 examples of caseous necrosis? |
|
Definition
|
|
Term
| What causes fat necrosis? |
|
Definition
| inappropriate release & activation of pancreatic lipases => breakdown of plasma membrane & intracellular triglycerides => saponification of calcium bound to the free fatty acids |
|
|
Term
| What is the gross appearance of fat necrosis? |
|
Definition
|
|
Term
| What is seen microscopically in fat necrosis? |
|
Definition
| hazy basophilic outlines of necrotic adipocytes with associated acute inflammation |
|
|
Term
| What's an example of fat necrosis? |
|
Definition
|
|
Term
| What causes fibrinoid necrosis? |
|
Definition
| vascular injury due to disorders => deposition of abundant fibrin |
|
|
Term
| What is seen microscopically in fibrinoid necrosis? |
|
Definition
| smudgy, hypereosinophilic appearance to the areas of necrosis typically involving small arteries, arterioles or capillaries |
|
|
Term
| What are 4 examples of fibrinoid necrosis? |
|
Definition
1) polyarteritis nodosa
2) malignant hypertension
3) hyperacute transplant rejection
4) rheumatoid nodules |
|
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