6. Cellular Response To Injuries Flashcards
Cellular response to injury: Hypoxia and ischemia
Deficiency in oxygen leads to failure of many energy dependent metabolic pathways and ultimately lead to cell death by necrosis
Failure of ATP generation and depletion of ATP in cells = necrosis
If only for a short time = apoptosis
Cell response to multiple injurious stimuli
Increase ROS - damage to lipids, proteins, nucleic acids - cell injury - necrosis (or apoptosis depending on type of ROS)
Cell response to mutations, cell stress and infections
Accumulation of misfolded proteins - apoptosis
Cellular response to radiation, other insults
Nucleus degradation - apoptosis
Cell response to infections, immunologic disorders
Inflammation - toxic molecules - necrosis or apoptosis
Hypoxia vs ischemia
hypoxia -Reduced oxygen supply less severe then ischemia
Ischemia - reduction in blood supply, no oxygen or other nutrients and no way to remove waste products - more damaging then hypoxia
Ischemia reperfusion injury
Injury due to restoration of blood flow to ischemia but viable tissues (MI, ARF, stroke)
Mechanisms of ischemia-reperfusion injury
Increase generation of ROS - some of mitochondria are dead/dying and do ineffective oxidative phosphorylation - mitochondria cannot properly reduce oxygen = ROS
Increase local inflammatory filtrate - bringing more blood and cells that increase inflammation
Complement activation - bind IgM antibodies that activate complement system = MAC created to stab microbes, but in this case stabs our own cells
Oxidative Stress
Induced by ROS - single unpaired election
Produced normally in small amounts in all cells during redox reactions also produced in phagocytosis leukocytes (neutrophils and macrophages)
Antioxidant system use to combat these, But is usually exhausted so there is an accumulation of ROS = damage
Mechanisms that produced ROA
ROS is like a bullet traveling through cell:
- Plasma membrane - damaged by causing peroxidation of lipid molecules present in plasma membrane
- Cytoplasm - break polypeptide chains and cause protein misfolding
- Nucleus- damage DNA causing strand breakage and mutations - p53 cause apoptosis through intrinsic pathway
Hypertrophy
An increase in size of cells - no new cells. Occurs in cells that cannot divide
Due to synthesis and assembly of additional intracellular structural components
Pathological - hypertension, induced cardiac HT
Physiological - bodybuilding, pregnancy
Hyperplasia
An increase in number of cells In an organ or tissue in response to a stimulus
Can only take place is tissue contains cells that are capable of dividing
Is a growth factor driven
Physiological - liver, bone marrow, breast
Pathological - thyroid (goiter), BPH
Atrophy
Opposite of hypertrophy
Reduction in the size of an organ or tissue due to a decrease in cell size and number
Cells are not DEAD - function is reduced and be restored (dystrophy is dead)
Causes of Atrophy
Decreased workload, loss of inner action, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, pressure
Decrease metabolic activity - decrease protein synthesis - increase protein degradation = atrophy
Metaplasia
Reversible change in whcih one adult cell type is replaced by another cell type - for protection can lead to cancer
Often represents an adaptive response in which one cell type that is sensitive to a particular stress is replaced by another cell type that can withstand adverse environment
