Chapter 2: Cell response to stress Flashcards
define hyaline change
alteration within a cell or ECM that causes a homogenous, glassy, pink appearance on histology stain.
-is not a particular pattern of accumulation and can be seen in connection to protein accumulation
difference of cellular response between cell injury by low O2 perfusion (hypoxic injury) or infection at the initial stage and late stage?
if acute= cell injury
initially: reversible, causes cellular swelling and increase fatty change (more adipose)
if chronic= cell death
late stage progression including DNA damage: irreversible, cell death by necrosis or apoptosis
what is hypoxic injury? and what are the 3 underlying mechanisms that cause it ?
hypoxic injury- result of low oxygen delivery to tissues (hypoxia) which decreases oxidative phosphorylation and decreases ATP production resulting in injury
- ischemia: low blood flow through organ
causes: 1 blocked arterial flow (atherosclerosis)
2. blocked venous drainage
3. shock (low blood tissue perfusion from decreased cardiac output) - low oxygen carrying capacity of blood
causes: 1. anemia (low RBC and therefore low Hgb)
2. CO poisoning (CO Hgb affinity > O2)
3. methemoglobinemia ( amount of Fe3+ > Fe2+) - hypoxemia: low oxygen content in blood due to hemoglobin loss or dysfunction (PaO2< 60mmHg)
casuses: 1. high altitude (decreased PAO2)
2. hypoventilation (increased PACO2)
3. COPD (increased PACO2)
what is a big indicator of irreversible cell injury that will progress to cell death
leakage of cellular proteins into blood causing an increase in blood levels that can be seen in lab work
two big characteristics that mark irreversibility of cell injury
- inability to reverse mitochondrial dysfunction
2. profound disturbances of plasma membrane
example of abnormal lipid accumulation
xanthomas
atheroscelrosis
cholesterolosis
neiman pick disease type C
pathologic effects of ROS formation
- lipid peroxidation –> membrane damage
- protein modification –> breakdown and misfolding
- DNA damage –> mutation
*Please Don’t Look
disorders of excessive cell death
- neurogenerative disorder
- ischemic injury
- stroke
- death of virally infected cell
hyperplasia is ____ driven
growth factor
what are the 2 types of pathologic calcification
- dystrophic calcification
2. metastatic calcification
define metastatic calcification
- calcium deposition in normal tissues (not necrotic) due to increases calcium (hypercalcemia) from Ca2+ metabolic dysfunctions
- usually not harmful unless severely progressive
- increased risk of tissues with alkaline compartments
cause of hemosideren accumulation
(hemosiderin = iron storage form)
excess iron being turned into hemosiderin granules by ferritin
- localized = tissue hemorrhage (causes bruising)
- systemic = hemosiderosis (caused by hemolytic anemia, hemochromatosis, or repeated blood transfusion )
*can be seen in coagulative necrosis by red infarction (organs with dual blood supply)
cellular swelling is seen in
reversible cell injury
and
necrosis
pathologic effects of defects in membrane permeability and membrane damage
- mitochondrial membrane damage (caspace activation)
- plasma membrane damage (leakage of cell content)
- lysosomal membrane damage (leakage of enzymes causing digestion of RNA, DNA, and glycogen leading to necrosis)
examples of exogenous pigment accumulation
carbon (can darken LNs and lungs)
tattoos
Key features and mechanisms of coagulative necrosis
- most commonly seen with extensive tissue injury due to ischemic infarction (all tissues except brain)
- firm; maintenance of cell/shape structure
- nucleus disappears
- can be red infarction (due to venous thrombi induced congestion and hypoxia) or white infarction (due to arterial thrombi induced occlusion and hypoxia)
- **wedged shaped pattern
function of glutathione peroxidase
removal of OH free radical
most dangerous ROS
define cholesterolsis
cholesterol- macrophages complex build up in lamina propria of the gall bladder
what are ways that the mitochondria can become damaged and cause progression of cell injury ? and what are the 3 major consequences of mitochondrial damage?
causes:
increased intracellular Ca2+ , ROS, toxins, or decreased O2 levels by hypoxic or chemical injury
consequences:
- formation of mitochondrial permeability transition pore (which contains cyclophilin D) leading to ox phos failure and depletion of ATP and necrosis
- abnormal Ox phos leads to ROS formation and necrosis
- leakage of cytochrome C which activates apoptosis
Atrophy results in decreased cell size in two ways. what are the differences between the mechanism of ubiquitin degradation pathway and autophagy ?
ubiquitin
- decrease in protein content of the cell by tagging with ubiquitin and activating lysosomal degradation activity
authophagy
- destruction of “self” cell organelles in 3 ways
1. macroautophagy: requires de novo formation of phagophore–>autophagosomes–>autolysosome which degrades cell.
2. microautophagy: direct lysosomal membrane invagination of cell organelle
3. chaperone mediated: chaperone transport of misfolded protein across lysosomal membrane
types of necrosis
coagulative liquefactive gangrene caseous fatty fibrinoid
mechanism of metaplasia ?
List common clinical examples
stem cell reprogramming causing surface epithelium or mesenchymal cells (cartilage, bone, blood vessels) to change cell types.
*can cause malignant transformation of metaplastic epithelium if the the reversible stimuli is not removed
Squamos metaplasia (from chronic smoking): respiratory tract columnar cells –> squamous cells
Barrets esophagus (from chronic GERD): lower esophageal squamous –> conciliated columnar with goblet (mucous secreting) cells
myosistiits ossificans: (from skeletal muscle inflammation by intermuscular hemorrhage) muscle –> boney cell types
Vitamin A deficiency: squamous metaplasia of respiratory tract, or keratomalacia (thicked eye conjunctiva by squamous cells)
what 2 types of adaptation are associated with malignant transformation
- metaplasia
- pathologic hyperplasia (common in response to viruses) - bc increased cell proliferation can occur if mutation of regulation occurs
function of catalase
decomposes H202 to H20 and O2
*removes H202
what is the cellular response to cell injury by cumulative sublethal/chronic injury over life span
cellular aging