Chapter 2 Part 2 Flashcards
What are the morphologic features of necrosis?
Increased eosinophilia (due to loss of cytoplasmic RNA and denatured proteins), more glassy than normal cells due to loss of glycogen, may appear moth eaten, will eventually become myelin figures that are degraded, DNA changes will also appear
Define karyolysis
basophilia of chromatin fades, reflects loss of DNA because of enzymatic degradation
Define pyknosis
Nuclear shrinkage and increased basophilia
Define karyorrhexis
pyknotic nucleus undergoes fragmentation
What is the morphology of coagulative necrosis?
Necrosis in which the architecture of the tissue is preserved, eosinophilic cells may persist but will be phagocytosed by leukocytes
What is the morphology of liquefactive necrosis?
Digestion of dead cells resulting in the transformation of tissue to liquid, often presents in CNS
What is the morphology of gangrenous necrosis?
limb that has lost its blood supply and has undergone necrosis
What is the morphology of caseous necrosis?
Structureless collection of lysed cells and amorphous granular debris enclosed by a border
What is the morphology of fat necrosis?
Focal area of fat destruction due to activated pancreatic lipases in peritoneal cavity, fatty acids combine with calcium to produce fat saponification
What is the morphology of fibrinoid necrosis?
Necrosis seen in immune reactions involving blood vessels, complexes of antigens and antibodies deposited in walls of arteries and produces a bright pink and amorphous fibrinoid
The cellular response to injury depend on what three things?
Nature of the injury, duration, and severity
The consequences of cell injury depend on what three things?
The type of cell, state, and adaptability
What are the two main pathways of ATP production?
Oxidative phosphorylation and glycolytic pathway
What are the major causes of ATP depletion?
reduced oxygen and nutrients, damage to mitochondria and the actions of toxins
How is the activity of the plasma membrane energy-dependent sodium pump effected by ATP depletion?
Causes an accumulation of sodium and water inside the cell, and diffusion of potassium out of the cell
How is cellular energy metabolism altered by ATP depletion?
Increase in anaerobic glycolysis by rapidly using glycogen stores and causing the build up of lactic acid and reducing the intracellular pH
How does a decrease in ATP alter protein production?
The loss of ATP causes a disruption of proteins involved in synthesis, a detachment of ribosomes from the ER, overall reducing protein synthesis
What are the three major consequences of mitochondrial damage?
Opening of mitochondrial permeability transition pore, abnormal oxidative phosphorylation and activation of caspases
What are the consequences of the opening of the mitochondrial permeability transition pore?
Loss of mitochondrial membrane potential resulting in an overall depletion of ATP
What is the main consequence of abnormal oxidative phosphorylation as it relates to mitochondrial damage?
The production of ROS
What is the main consequence of caspase activation as a result of mitochondrial damage?
apoptosis
What are the main mechanisms of cellular injury due to Ca influx?
The opening of mitochondrial membrane permeability pores, activation of enzymes such as phospholipases, proteases, endonucleases, and ATPases, and ultimately the activation of apoptosis (caspases)
What is a reactive oxygen species? Examples?
Oxygen-derived free radical; superoxide anion, hydrogen peroxide, hydroxyl anions
How are free radical generated?
ReDox reactions in normal metabolic processes, absorption of radiation, leukocytes in inflammation, metabolism of exogenous chemicals, presence of transition metals
How are free radicals removed?
Antioxidants, free iron or copper, and enzymes
How is superoxide anion produced?
Incomplete reduction of oxygen during oxidative phosphorylation and by leukocytes
How is superoxide anion inactivated?
Converted to hydrogen peroxide and oxygen by superoxide dismutases
What are the pathological effects of superoxide anion?
Stimulates the production of enzymes that cause degradation, and may directly damage cell structures
How is hydrogen peroxide produced?
Generated by superoxide dismutase from superoxide anion and by oxidases in peroxisomes
How is hydrogen peroxide inactivated?
By conversion to water and oxygen by catalase in peroxisomes or by glutathione peroxidase in the cytosol or mitochondria
What are the pathological effects of hydrogen peroxide?
Can be converted to hydroxyl radical or hypochlorite, destroying microbes and cells
How is the hydroxyl radical produced?
Generated from water by hydrolysis
How is the hydroxyl radical inactivated?
Conversion to water by glutathione peroxidase
What are the pathologic effects of hydroxyl radical?
Damages lipids, proteins, and DNA
How is peroxynitrite produced?
interaction of superoxide anion with nitric oxide
How is peroxynitrite inactivated?
converted to nitrite (HNO2) by peroxiredoxins
What are the pathological effects of peroxynitrite?
Damages lipids, proteins, DNA
What are the main mechanisms of membrane damage?
ROS, decreased phospholipid synthesis, increased phospholipid breakdown, and cytoskeletal abnormalities
What are the consequences of plasma membrane damage?
Loss of osmotic balance and influx of fluids and ions
What are the consequences of injury to lysosomal membranes?
Leakage of enzymes into cytoplasm and activation of hydrolases, resulting in enzymatic damage to cells
What are the two characteristics of irreversible cell damage?
Inability to reverse mitochondrial dysfunction, profound disturbances in membrane function
Why can tissue specific cell injury be detected?
Damaged cell membranes cause the leakage of intracellular proteins into systemic circulation
Describe lipid peroxidation in membranes
Oxidative damage is initiated when double bonds in unsaturated fatty acids of lipids are attacked by ROS, resulting in peroxides
Describe oxidative modification of proteins
Free radicals cause the oxidation of amino acid side chains and protein backbone, resulting in the changes of their bonds and interactions, leading to misfolding
Describe the pathological effects of free radicals as it relates to lesions in DNA
Free radicals are capable of causing breaks and cross-linking in DNA
What is the mechanism of cell injury due to mild ischemia?
Reduced oxidative phosphorylation results due to decreased oxygen and nutrient availability. This decreased the amount of ATP and causes the failure of the Na pump and an influx of sodium and water. This leads to cell and organelle swelling.
What is the mechanism of cell injury due to prolonged ischemia?
Severe mitochondrial swelling and calcium influx, lysosomal rupture, death by necrosis due to the release of cytochrome C
What is the mechanism of cell injury due to reperfusion?
Blood brings calcium that overloads injured cells and causes mitochondrial injury, free radicals and cytokines induced by leukocytes, local activation of complement results
