Cell Injury, Death, and Adaptation Flashcards
Exam I
Etiology categories of injurious agents causing cell injury/death/adaption
ATP depletion
Oxygen and oxygen-derived free radicals
Intracellular calcium and loss of calcium steady state
defects in membrane permeability
Karyorrhexis
fragmentation of nuclear material
Pyknosis
clumping of nuclear material
Karyolysis
dissolution of nuclear material
Cellular outcome of Na/K pump failure
Sodium ions enter freely (accompanied by water), potassium ions leave freely, and calcium ions gain abnormal entry into the cell and the intracellular organelles
When the cell swells, all of the organelles within the cell (which are also membrane-bound) swell
When the rough ER swells (where protein synthesis occurs), the ribosomes fall off and protein synthesis stops
Cellular outcome of lactic acid buildup
Lactic acid buildup causes the intracellular pH to decline, incapacitating cells (which function within a very narrow range of pH)
Leads to: Pyknosis, karyorrhexis, and karyolysis and the rupture of already swollen lysosomes
Lysosomes release their proteolytic enzymes, which autodigest cell contents and the cell membrane
Disruption of the cell membrane increases calcium influx into the cell/organelles and causes release of cellular contents into the tissue spaces and blood (extracellular fluid)
Results of excessive free intracellular calcium
This excessive free calcium activates proteases, endonucleases, and phospholipases that proceed to destroy the cell and its contents
Reperfusion injuries
Occur when blood flow is restored to tissue that has been anoxic and functioning under anaerobic metabolism
Restoration of blood flow causes a burst of oxidative metabolism and accumulation of oxygen free radicals
Free radicals
Unstable compounds with an unpaired electron in their outer ring, making them anxious to react with other substances
Normal byproducts of cellular metabolism that are always present in the body
Have a particular affinity for lipid substances
Free radical effect on cell membranes
Free radicals combine avidly with cell or organelle membranes and “drill a hole”, or have a phosphokinase-like effect
This binding results in the dissolution of the membrane and chain reactions of toxic byproduct production, in an effect called lipid peroxidation
Reactive oxygen species (ROS)
A subset of free radicals that contain oxygen (oxygen-based free radicals)
Formed as natural oxidant species in cells during mitochondrial respiration and ATP generation
Free radical removal
antioxidants
Endogenous agents
Normally found in the body
Exogenous agents
Not normally found in the body
Chronic alcoholism and lipids
increases the conversion of FFA to triglycerides
Cause of liver fat accumulation
Increased mobilization and delivery of free fatty acids to liver cells can result in fat accumulation
Unconjugated bilirubin
Fat-soluble and cannot be eliminated through the kidneys (urine)
Gradually released from macrophages into the plasma and combines with plasma albumin to transport to the liver
Taken up by liver cells and conjugated
Conjugated bilirubin
Water-soluble and can be eliminated through urine
As the concentration of conjugated bilirubin in liver cells increases, it begins to diffuse out of the cell and into the blood (down its concentration gradient)
In addition, some of the conjugated bilirubin becomes part bile, which exits liver cells through the hepatic duct –> common bile duct –> into the duodenum
Once in the intestines, half of the conjugated bilirubin is converted by bacterial action into urobilinogen, which is highly soluble
In the feces, it becomes altered and oxidized to form stercobilin (gives stool brown color)
About 5% is excreted by the kidneys into the urine and becomes oxidized to urobilin (gives urine yellow color)
Hemolytic jaundice
Excessive hgb breakdown and delivery of unconjugated bilirubin to the liver
Unconjugated bilirubin accumulates in plasma
Bilirubin absent in urine
Urobilinogen increased in urine and feces
Hepatocellular jaundice
Liver disease state
Unable to uptake, conjugate, &/or excrete bilirubin
Severe elevation of serum bilirubin
Conjugated and unconjugated bilirubin in plasma
LFTs abnormal
Obstructive jaundice
Obstruction to the flow of bile
Conjugated bilirubin accumulates in the liver and diffuses into the blood
Clay-colored stools (no bilirubin through intestines) and dark urine (how most of the conjugated bilirubin is excreted)
Hyperbilirubinemia outcomes
CNS toxicity
Kernicterus
significant neurological deficits or death due to hyperbilirubinemia
Cell necrosis
Uncontrolled, irreversible cell injury and eventual cell death due to pathological processes
A pathologic, disorganized sequence of events that results in swelling of cell organelles, plasma membrane rupture, and eventual lysis of cells and stimulates the inflammatory process
Coagulative necrosis
Most common type
Cell architecture remains preserved and tissue is usually replaced by scar/fibrous tissue
Gangrene is a subset (results from interruption of arterial blood supply to a tissue)
Dry gangrene
An area is free of infection and in which the line of demarcation between live and dead tissue is apparent
Tissue undergoing dry gangrene becomes dry and shrunken (mummified)
Wet gangrene
A combination of coagulative AND liquefactive necrosis
Infection is present in the area between live and dead tissue
The presence of an acute inflammatory reaction and inflammatory exudate are responsible for the “wet” component
Often malodorous, and the line of demarcation between live and dead tissue is unclear until the infection is arrested
Gas gangrene
Wet gangrene caused by Clostridium perfringens, an organism that produces gas within the destroyed tissue
Liquefactive gangrene
Most commonly observed in the CNS, and can occur in bacterial infections (pus)
Dying cells are digested by hydrolytic enzymes and lose their structural integrity, turning into a viscous mass
Formation of cysts
Fat gangrene
Occurs in acute pancreatitis when pancreatic enzyme release leads to liquefaction of the fat cells in the peritoneal cavity
Saponification
Caseous gangrene
“Cheesy”
Takes place in tuberculosis infection
Necrotic area is referred to as a granulom
Apoptosis
Type I programmed cell death
Genetically controlled, but can be physiologic or pathologic
Initiated by activation of caspase enzymes
○ Apoptosis components:
§ Promoter: p53
§ Bcl-2
§ Apaf-1
§ Caspase 9
§ Cytochrome c
Eliminates individual cells, which are normally phagocytized
Not associated with inflammation
Autophagy
Type II programmed cell death
A survival mechanism that salvages key metabolites to promote homeostasis (garbage collecting and recycling)
Atrophy
A reduction in cell size and reversion to a lower and more efficient level of functioning
Occurs in response to a decrease in work demands or adverse environmental condition
Hypertrophy
An increase in cell size and functional components within the cell resulting in an increase in tissue size
Occurs in response to an increase in work demands
Hyperplasia
An increase in the number of cells in an organ or tissue that is still capable of mitotic division
Occurs in response to an increase in work demands
Metaplasia
The substitution of one type of normal cell with another type of normal cell, but one that is not normally found in that tissue
The replacement cells are better able to survive under stressful circumstances
Often occurs in response to chronic irritation
Dysplasia
Characterized by deranged cell growth and differentiation within a specific tissue, resulting in disorderly cells that vary in size, shape, and appearance
Preneoplastic
Causes of aging
Thought to be a result of an accumulation of DNA and metabolic (free radical) damage
Cells may age more quickly when DNA repair mechanisms are faulty and when metabolic damage is excessive because of reduced antioxidants
Possible genetic, epigenetic, inflammatory, oxidative stress, and metabolic origins
Diet is thought to play a major role in the development of age-related disease
Associated with inflammation, hypercoagulability, and immune changes
May involve an increase in autoantibodies and damage accumulation
Cross-linking theory of aging
Decrease in cell permeability
