PATH:Reversible Cell Injury and Cellular Adaptation Flashcards
What is the difference between ischemia and hypoxia? What is an example of a case when hypoxia can exist without ischemia?
Ischemia refers to a lack of blood flow, while hypoxia refers to a lack of oxygen; CO poisoning would induce hypoxia but not ischemia
How can a lack of oxygen lead to ATP depletion?
The majority of ATP in a cell is made through oxidative phosphorylation- without oxygen, this process cannot occur. Though ATP can still be generated through the glycolytic pathway, it is not enough
How do reactive oxygen species cause cellular damage?
By causing damage to proteins, lipids, DNA
How do defects in membrane integrity cause cell injury?
Decreased membranal integrity leads to increased permeability and a decreased ability of the cell to maintain ion concentrations and homeostasis
How does increased intracellular [Ca++] cause cellular damage?
Activation of cellular enzymes including lipases that can break down cellular constituents and organelles, resulting in membranous damage, nuclear damage and ATP depletion
What two organelles serve as major calcium stores?
Mitochondria and sER
What is the Mitochondrial Permeability Transition Pore?
Pores that are generated on the internal mitochondrial membrane in response to damage, which interrupts oxidative phosphorylation
What component of the inner mitochondrial membrane, if released into the cytoplasm, is a potent pro-apoptotic stimulus?
Cytochrome c
How can mitochondrial damage lead to either apoptosis or necrosis?
Cytochrome c and other pro-apoptotic proteins released from the mitochondria can initiate the apoptotic pathway; severe ATP depletion can cause necrosis
Is ischemia/hypoxia a source of reversible or irreversible cell damage?
It is reversible if reversed in time, however, prolonged ischemic/hypoxic injury will lead to irreversible damage
What are the reversible changes that are induced by acute ischemia/hypoxia?
Decreased membrane transporter activity secondary to decreased ATP, which results in influx of Na+ and H2O and cellular swelling; Decreased oxidative phosphorylation stimulates an increase in glycolytic pathway activity, lactic acid accumulation, and decreased pH which can alter enzymatic activity, protein structure, chromatin clumping; Decreased protein synthetic function (detachment of ribosomes from rER); Altered cytoskeletal elements (loss of micovilli, blebbing); Functional aspects of differentiated cells may cease
What is hyperplasia?
An increase in number of cells in an organ
What is hypertrophy?
An increase in the size of a cell
What are three examples of physiologic hyperplasia?
1) Hormonal (estrogen) stimulation of endometrium during menses 2) Increased size and # of glands and smooth muscle cells of pregnancy-associated organs 3) Removal of 1/2 of the liver–> rapid cell division and differentiation
What are two examples of physiologic hypertrophy?
1) exercise results in increased size of skeletal muscle cells 2) remove a kidney and the contralateral kidney shows increased size of glomeruli and tubules (compensatory hypertrophy)
What pathologic cellular adaptation occurs in the heart in response to extra demand, usually due to hypertension or valvular heart disease?
Pathologic hypertrophy
What are 2 examples of pathologic hyperplasia?
Endometrial hyperplasia, chronic renal failure–> parathyroid hyperplasia
What are the major mechanisms of hyperplasia and hypertrophy?
Hormone or growth factor over-stimulation, and increased functional demand
What is atrophy?
Decrease in cell size and volume; decrease in cell number; decreased size/weight of an organ
What is physiologic atrophy
A decrease in size of embryologically formed structures primarily through apoptosis
What are three types of pathologic atrophy?
Disuse atrophy- secondary to decrease in workload; Denervation atrophy- cutting nerves to skeletal muscles ; Ischemic atrophy- gradual reduction in blood supply over time
What are the mechanisms that result in atrophy?
Down-regulation of protein synthesis, increased proteolysis via proteasome, and autophagy
What is metaplasia?
A change in differentiation of cells forming tissue not normally present in that anatomic site
What is squamous metaplasia and what is a common example of this?
Transformation of different epithelium into “tough” stratified squamous epithelium; Barret’s esophagus or cigarette smoke irritation
What is the mechanism of metaplasia?
Reprogramming of stem cells brought about by growth factors or cytokines
