2 - Biochemical Mechanisms Associated With Injury (Exam 1) Flashcards
Is ATP necessary for anabolic processes?
Yes, and if there are not adequate levels of ATP, these processes will be reduced.
What are 4 examples of anabolic processes?
- Protein and nucleic acid synthesis
- Membrane transport mechanisms
- Maintenance of cellular osmolarity
- Intracellular homeostatic mechanisms
What is 1 example of a Reactive Oxygen Species?
Free radicals
Briefly explain free radicals
They are highly reactive and damaging to cells
What are the generally normal concentrations for calcium inside the body?
Higher concentrations in the extracellular space, stored in specific intracellular structures when present in the cell.
How does injury change calcium concentrations?
Calcium ions can freely enter the cell and can also release calcium from intracellular stores.
What 2 changes can result from a changes in plasma membrane permeability?
- Loss of concentration gradients
2. Abnormal movement of solute and water
What changes can occur as a result of mitochondral damage?
Formation of high conductance channels of the inner mitochondrial membrane causes damage to proton gradient across mitochondrial membranes. This results in decreased oxidative phosphorylation and therefore decreased ATP production.
What are 3 common forms of cell injury?
- Ischemic
- Hypoxic
- Free-radical induced
Ischemic and hypoxic are very similar
What is the most common type of cell injury?
Ischemia
Which injures tissues faster, ischemia or hypoxia?
Ischemia
How does ischemia differ from hypoxia?
Less blood leaves the tissue resulting in less removal of metabolic byproducts.
What is hypoxia?
Reduced delivery of oxygen, below the demands of the tissue.
What are 4 effects of both ischemia and hypoxia?
- Cellular Swelling
- Increase in anaerobic glycolysis
- Decrease in pH as a result of lactic acid production
- Detachment of ribosomes from rough ER - because of decreased pH and ATP
What are free radicals?
Chemical species that have a single unpaired electron in the outer orbit, extremely reactive and unstable.
What are 3 sources of free radicals?
- Absorption of extreme energy by the cell, such as ionizing radiation.
- Endogenous reactions associated with reduction of oxygen to water (normal, but excess is bad).
- Enzymatic metabolism of exogenous chemicals/ drugs.
How does the body eliminate free radicals?
The cell’s scavenger system (associated with ER) picks up/ releases electrons.
What are 3 examples of scavenging system compounds?
- Catalases
- Superoxide dismutase
- Glutathione peroxidase
What are 7 examples of antioxidant chemicals that can either block formation of or inactivate free radicals?
- Vitamin C
- Vitamin E
- Cysteine
- Glutathione
- Albumin
- Ceruloplasmin
- Transferrin
What is 1 example of cellular injury caused by free radicals?
Lipid Peroxidation
What is a brief summary of lipid peroxidation?
Destruction of polyunsaturated lipids
This leads to membrane damage and increased permeability and can increase the formation of free fatty acids (precursors to inflammatory molecules).
Damage can be caused to critical proteins, DNA, and mitochondria.
What are 7 types of accumulations associated with cell injury?
- Water
- Proteins
- Lipids
- Cholesterol
- Glycogen
- Pigments
- Minerals
What occurs when water accumulates in the cell?
Results in “cloudy swelling” or hydropic degeneration.
Usually associated with damage to the plasma membrane.
What is steatosis, and what is it a sign of?
The abnormal accumulation of triglycerides within cells.
Usually a sign of reversible damage, may occur in cells adjacent to necrotic cells.
What are 3 causes of cellular lipid accumulation?
- Excessive lipid load (obesity)
- Inability to metabolize normal amounts of lipids
- Excessive lipid mobilization (diabetes, protein malnutrition)
What are 2 causes of cellular protein accumulation?
- Increased exposure of proteins
2. Increased protein synthesis
What are 2 causes of cellular glycogen accumulation?
- Glucose/glycogen metabolism problems
2. Genetic disorders - glycogen storage disease
What are two types of pigments?
- Exogenous
2. Endogenous
What is 1 example of an exogenous pigment?
Carbon from coal dust
What are 2 example of endogenous pigments?
- Melanin
2. Hemosiderin
What is melanin?
Brown-black pigment formed in melanocytes
Can be accumulated in skin and dermis from sun exposure
Often formed by tyrosine
What is hemosiderin?
Golden yellow pigment derived from hemoglobin
Accumulates in tissues with excess of iron
Localized accumulation leads to bruising
What are 3 examples of cellular mineral accumulation?
Accumulation of:
- Foreign particulate matter leads to pneumoconiosis
- Coal dust leads to anthracosis
- Asbestos leads to asbestosis
What is metastatic calcification?
Deposition of calcium in normal tissue, due to hypercalcemia
What are 4 main causes of metastatic calcification?
- Increase in parathyroid hormone production
- Bone destruction - tumors
- Vitamin D intoxication
- Renal failure - associated with secondary hyperparathyroidism - excess calcium absorption
What is dystrophic calcification?
Deposition of calcium in necrotic tissues, causes structural dysfunction as seen in:
Atherosclerosis - dystrophic calcification of blood vessels and heart valves
What are the 2 types of cell death?
- Apoptosis
2. Necrosis
What is necrosis?
The dissolution of the cell after death
What are 2 things necrosis can result from?
- Autolysis (cellular self digestion)
2. Heterolysis (digestion from lysosomes of invading cells)
What are 4 patterns of necrosis?
- Karyolyis - nuclear swelling, gradual loss of chromatin
- Pyknosis - Clumping of nuclear material and increased basophilia
- Karyorrhexis - Fragmentation of pyknotic nucleus
- Karyohexis - Complete loss of nuclear material
What are the 5 types of necrosis?
- Coagulative Necrosis
- Liquefaction Necrosis
- Gangrenous Necrosis
- Caseous Necrosis
- Fat Necrosis
What are the 3 types of gangrenous necrosis?
- Dry gangrene
- Wet gangrene
- Gaseous gangrene
What is coagulative necrosis?
Preservation of structural outline of cell/tissue for a number of days, general architecture preserved.
Likely to occur in areas of hypoxia caused by ischemia or chemical injury
Protein albumin changes to firm, opaque state
What is liquefaction necrosis?
Associated with ischemic injury to neurons/glial cells
Can also occur alongside staph/strep infections
Tissue becomes soft, liquefies and forms cyst
What is gangrenous necrosis?
Combination of coagulative and liquefaction necrosis, microbes may or may not be present.
What is dry gangrene?
Generally only coagulative necrosis
Skin/tissue dries, shrinks, and turns dark
What is wet gangrene?
Occurs when neutrophils invade tissue and cause liquefaction necrosis.
Occurs mainly in internal organs, causes site to become cold, swollen, and dark.
Foul smell may come from bacteria.
What is gaseous gangrene?
Associated with an invasion of the Clostridium species.
Foul smelling infections, death may occur from systemic toxemia
What is caseous necrosis?
Caused by mycobacterium, corynobacterium, and fungi
Combination of coagulative and liquefaction necrosis
Dead cells disintegrate, but are not digested, resulting in what looks like cottage cheese.
What is fat necrosis?
Occurs in the breasts, pancreas, and abdominal muscles
Free fatty acids combine with cations resulting in saponification
Tissue appears opaque and white like soap.
What is apoptosis?
Programmed cell death - occurs normally
Usually affects single cells
Does not result in loss of function
