Flashcards in Cell Response to Stress and Toxic Insult Deck (50):
Increase in size of an organ or tissue due to an increase in the SIZE of cells.
Hypertrophy- include an increase in protein synthesis and an increase in the size or number of intracellular organelles
What is exemplified by the increase in skeletal muscle mass associated with exercise and the enlargement of the left ventricle in hypertensive heart disease?
Increase in the size of an organ or tissue caused by an increased in the NUMBER of cells.
What is exemplified by glandular proliferation in the breast during pregnancy?
What is a failure of cell production?
During fetal development, aplasia results in ______, or absence of an organ due to failure of production.
What is a decrease in cell production that is less extreme than in aplasia?
Hypoplasia- seen in the partial lack of growth and maturation of gonadal structures in Turner syndrome and Klinefelter syndrome
What is a decrease in the size of an organ or tissue and results from a decrease in the MASS of preexisting cells?
Causes of atrophy
Most often- disuse, nutritional or oxygen deprivation, diminished endocrine stimulation, aging, and denervation
What is atrophy thought to be mediated in part by?
The ubiquitin-proteasome pathway of protein degradation
The ubiquitin-linked proteins are degraded within the proteasome, a large cytoplasmic protein complex
What is the replaced of one differentiated tissue by another?
Where can squamous metaplasia occur?
The cervix, respiratory epithelium of the bronchus, in the endometrium, and in the pancreatic ducts
Associated conditions with metaplasia? Reversible?
Chronic irritation and vitamin A deficiency
Yes it is often reversible
What results from cellular anoxia or hypoxia which in turn results from various mechanisms including what? (5)
Hypoxic cell injury
1. Ischemia (most common cause)
3. Carbon monoxide poisoning (results in diminution in the oxygen-carrying capacity of RBC by chemical alteration of hemoglobin)
4. Decreased perfusion (cardiac failure, hypotension, and shock)
5. Poor oxygenation (secondary to pulmonary disease)
Hypoxic cell injury first affects the ____, which leads to decreased _____ _____ and _____ synthesis.
Mitochondria, oxidative phosphorylation, ATP
What are 3 consequences of decreased ATP availability?
1. Failure of the cell membrane pump which leads increased intracellular Na+ and water and decreased intracellular K+ therefore leading to to cellular swelling, swelling of the ER, and swelling of the mitochondria
2. Disaggregation of ribosomes leading to failure of protein synthesis
3. Stimulation of phosphofructokinase activity resulting in increased glycolysis, accumulation of lactate, and decreased intracellular pH
Hypoxic cell injury eventually results in ____ _____ to plasma and to lysosomal and other organelle membranes with loss of membrane phospholipids.
Reversible morphological signs of damage include the formation of what 2 things?
1. Myelin figures- whorl-like structures, originating from damaged membranes
2. Cell blebs- a cell surface deformity most likely caused by disorderly function of the cellular cytoskeleton
What is caused by severe or prolonged injury?
The point of no return is marked by irreversible damage of cell membranes leading to ____ _____ _____, extensive calcification of the ______, and cell death.
Massive calcium influx, mitochondria
Intracellular enzymes and various other proteins are released from ____ _____ into the circulation as a consequence of the loss of integrity of cell membranes. (Ex. MI)
Hypoxic injury becomes irreversible after _____ for neurons and _____ for myocardial cells and hepatocytes. Many hours for _____ cells.
3-5 minutes for neurons(purkinje cells of cerebellum and neurons of the hippocampus more susceptible)
1-2 hours for myocardial cells and hepatocytes
Many hours for skeletal muscle cells
What are the 6 mechanisms that generate free radicals?
1. normal metabolism
2. oxygen toxicity
3. ionizing radiation
4. ultraviolet light
5. drugs and chemicals
6. reperfusion after ischemic injury
How do drugs and chemicals generate free radicals?
they promote proliferation of the smooth ER and induction of the P-450 system of mixed function oxidases of the SER
What are the 3 mechanisms that degrade free radicals?
1. intracellular enzymes (glutathione peroxidase, catalase, and superoxide dismutase 2)
2. exogenous and endogenous antioxidants (vit. A, C, E, cysteine, glutathione, selenium, ceruloplasmin, and transferrin)
3. spontaneous decay
CCl4 is processed by the _____ system of mixed function oxidases with the SER, producing the high reactive free radical ____.
P-450 system, CCl3-
CCl3- diffuses throughout the cell, initiating lipid peroxidation of intracellular membranes and widespread injury results
CCl3- results in widespread injury including what 2 things?
1. Disaggregation of ribosomes resulting in decreased protein synthesis (leads to accumulation of intracellular lipids)
2. Plasma membrane damage caused by products of lipid peroxidation in the SER (results in cell swelling and massive influx of Ca --> mitochondrial damage, denaturation of cell proteins, and cell death)
What is the sum of the degradative and inflammatory reactions occurring after tissue death caused by injury (eg. hypoxia and exposure to toxic chemicals)?
____ refers to degradative reactions in cells caused by intracellular enzymes indigenous to the cell.
Autolysis- postmortem autolysis occurs after the death of the entire organism and is NOT necrosis
____ refers to cellular degradation by enzymes derived from sources extrinsic to the cell (eg. bacteria and leukocytes).
What type of necrosis is most often from a sudden cutoff of blood supply to an organ (ischemia)? What 2 organs particularly?
coagulative necrosis in the heart and kidney
When is general preservation of tissue architecture characteristic?
the early stages
Why does increased cytoplasmic eosinophilia occur in coagulative necrosis?
protein denaturation and a loss of cytoplasmic RNA
What are the 3 morphologic hallmarks of irreversible cell injury and necrosis?
1. pyknosis (chromatin clumping and shrinking)
2. karyorrhexis (fragmentation of chromatin)
3. karyolysis (fading of chromatin)
What type of necrosis has ischemic injury to the CNS?
liquefactive necrosis- characteristically results in liquafactive necrosis (after death of CNS cells, liquefaction is caused by autolysis)
What type of necrosis occurs as part of granulomatous inflammation and is a manifestation of partial immunity caused by the interaction of T lymphocytes, macrophages, and probably cytokines?
What is the leading cause of caseous necrosis?
What combines features of both coagulative necrosis and liquefactive necrosis?
On gross examination, caseous necrosis has a _____ consistency. On histologic examination, caseous necrosis has an ______ ______ appearance.
amorphous eosinophilic appearance
What type of necrosis most often affects the lower extremities or bowel and is secondary to vascular occlusion?
When complicated by infective heterolysis and CONSEQUENT liquefactive necrosis, gangrenous necrosis is called ___ necrosis. When characterized primarily by coagulative necrosis WITHOUT liquefaction, gangrenous necrosis is called ____ necrosis.
What type of necrosis is a deposition of fibrin-like proteinaceous material in the arterial walls and appears smudgy and acidophilic?
fibrinoid necrosis- most often associated with immune-mediated vascular damage
What type of necrosis occurs after a severe injury to tissue with high fat content such as the breast?
traumatic fat necrosis
What type of necrosis is a complication of acute hemorrhagic pancreatitis?
enzymatic fat necrosis
Programmed cell death is also called what?
apoptosis- an important mechanism for the removal of cells
Morphologic features of apoptosis (5)
-tendency to involve single isolated cells
-lack of inflammatory response
-blebbing of plasma membrane, cytoplasmic shrinkage, and chromatin condensation
-budding of cell and separation of apoptotic bodies
-phagocytosis of apoptotic bodies
Which pathway of initiation is mediated by cell surface receptors exemplified by FAS?
the extrinsic pathway- the FAS ligand signals a series of events that involve activation of caspases
Which pathway is initiated by the loss of stimulation by growth factors and other averse stimuli resulting in the inactivation and loss of bcl-2 and other antiapoptotic proteins from the inner mitochondrial membrane?
intrinsic or mitochondrial pathway- results in increased mitochondrial permeability, the release of cytochrome c, and the stimulation of proapoptotic proteins such as bax and bak
What is characterized by direct activation of caspases by granzyme B?
cytotoxic T-cell activation- directly activates the caspase cascade